Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy.

The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.

Collagenous enterocolitis: a case of collagenous colitis with involvement of the small intestine.

A 78-yr-old previously well caucasian female presented with a 6-wk history of profuse watery diarrhea and weight loss. Clinical investigation showed evidence of mild malabsorption. Multiple biopsies of colonic mucosa revealed a wide subepithelial band of collagen typical of collagenous colitis. Duodenal biopsies showed similar collagen deposition and partial villous atrophy. Some amelioration of symptoms occurred with sulfasalazine therapy. This is the first reported case of collagenous colitis with histological evidence of small intestinal involvement. At least in some patients, collagenous colitis and collagenous sprue appear to be manifestations of a single disease. For such cases, the term collagenous enterocolitis is suggested.

Annular pancreas: a clinical, endoscopic, and immunohistochemical study.

A patient with annular pancreas presenting with severe upper abdominal pain is discussed. Endoscopic retrograde cholangiopancreatography (ERCP) was diagnostic, with successful injection of major and minor papillae showing pancreas divisum, an annular duct emptying at the major papilla and changes of severe chronic pancreatitis in all duct systems. Pylorus preserving pancreatoduodenectomy gave complete pain relief. The annulus was shown immunohistochemically to be entirely of ventral gland origin. Chronic pancreatitis was histologically less severe in the dorsal gland. Antegrade dye injection with x-ray showed dorsal to ventral connection in the resected specimen.

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.

Serum pepsinogen I and IgG antibody to Campylobacter pylori in non-specific abdominal pain in childhood.

A consecutive series of 51 children (mean age 11 years) who presented with recurrent abdominal pain were investigated by upper gastrointestinal endoscopy including three antral biopsies for microscopy, culture and urease testing. Serum IgG, IgA, and IgM antibodies to Campylobacter pylori (C pylori) were measured by the ELISA technique. Serum pepsinogen I was also measured. Thirty two children showed histological evidence of gastritis. All had C pylori on microscopy and or culture. Nineteen children showed no histological gastritis nor evidence of C pylori on microscopy, culture and/or urease testing. The IgG and IgA antibody levels to C pylori were significantly higher in C pylori positive children than in the negative group (p less than 0.001). Serum pepsinogen I concentrations were also significantly higher in C pylori positive children than in negative (p less than 0.001). Measurement of IgG antibody levels, combined with serum pepsinogen I estimation, predict the presence of C pylori associated gastritis in children with a sensitivity and specificity of up to 95%. It may be used therefore to predict gastritis and even peptic ulceration in children presenting with non-specific upper abdominal pain.

Occult carcinoma in an adult choledochal cyst.

The complications of choledochal cyst are avoidable if diagnosed early, and adequate resection undertaken. This case report describes the long history of right subcostal pain in a young man of 26 who had a squamous carcinoma in a choledochal cyst diagnosed after serial section of the excised cyst. Subsequent resection of the head of the pancreas showed histological residual tumour from which he died 4 months later. This case illustrates the need for complete early excision of a choledochal cyst to prevent this complication.

A 10 year single centre experience of percutaneous and endoscopic extraction of bile duct stones with T tube in situ.

A non-randomised single centre study of 226 consecutive patients referred over 10 years with retained common bile duct stones and a T tube in situ or a cholecystostomy tube are reported. Percutaneous extraction was attempted in 204 and endoscopic extraction in 68 patients. Percutaneous clearance was achieved in 158 (77.5%) patients and endoscopic clearance in 52 (76.5%) patients. Six of 153 (3.9%) patients followed after percutaneous treatment suffered major complications (pancreatitis, cholangitis, or tract perforation). Three of 67 (44%) patients followed after endoscopic treatment suffered major complications (pancreatitis, cholangitis, or bleeding). When the initial method of treatment failed, the alternative was used, resulting in an overall success rate of bile duct clearance of 94.3%. It is concluded that percutaneous and endoscopic methods of bile duct clearance in patients with a T tube in situ are equally effective, carrying similar complication rates. This study has helped to clarify the indications and efficacy of these alternative treatments.

Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction.

The development of non-surgical techniques for the relief of malignant low bileduct obstruction has cast doubt on the best way of relieving jaundice, particularly in patients fit for surgery whose life expectancy is more than a few weeks. We did a randomised prospective controlled trial comparing endoscopic stent insertion and surgical biliary bypass in patients with malignant low bileduct obstruction. 204 patients were randomised (surgery 103, stent 101); 3 subsequently proved to have benign disease and were excluded, leaving 101 surgical and 100 stented patients for assessment. Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. In stented patients, there was a lower procedure-related mortality (3% vs 14%, p = 0.01), major complication rate (11% vs 29%, p = 0.02), and median total hospital stay (20 vs 26 days, p = 0.001). Recurrent jaundice occurred in 36 stented patients and 2 surgical patients. Late gastric outlet obstruction occurred in 17% of stented patients and 7% of the surgical group. Despite the early benefits of stenting there was no significant difference in overall survival between the two groups (median survival: surgical 26 weeks; stented 21 weeks; p = 0.065). Endoscopic stenting and surgery are effective palliative treatments with the former having fewer early treatment-related complications and the latter fewer late complications.

Sclerosing cholangitis in acquired immunodeficiency syndrome. Case reports and review of the literature.

Four patients with acquired immunodeficiency syndrome (AIDS) (CDC group IV) were investigated for biliary disease because of the presence of both severe upper abdominal pain and raised levels of serum alkaline phosphatase. None was clinically jaundiced. Upper abdominal ultrasound was abnormal in three. All had endoscopic retrograde cholangiographic evidence of both an intrahepatic sclerosing cholangitis suggestive of primary sclerosing cholangitis and an irregular suprapapillary common bile duct dilation suggestive of papillary stenosis. Three had evidence of gastrointestinal cryptosporidiosis and two of disseminated cytomegalovirus infection. Endoscopic sphincterotomy, performed in two patients, gave good pain relief. We propose the name 'AIDS sclerosing cholangitis' for this form of secondary cholangitis. The cause of this disorder remains unclear. Recent evidence is discussed which suggests that it is not due to HIV itself but to an opportunistic infection. Cryptosporidium appears to be the most likely candidate.

Endoscopic endoprosthesis insertion following failure of cholecystojejunostomy in pancreatic carcinoma.

Sixteen patients in whom malignant biliary obstruction recurred after failure of cholecystojejunostomy had attempted relief of obstruction by endoscopic insertion of an endoprosthesis. This treatment was successful in 13 patients, although one required percutaneous insertion because of duodenal distortion and one required a combined percutaneous-endoscopic approach. Median survival after stenting was 3.5 months (range from 2 weeks to 16 months). Of the three treatment failures, two patients had external drainage only and one succumbed before further treatment could be attempted. There were two complications associated with the procedure (one small bile leak and one episode of cholangitis) but the 30-day mortality rate of 12.5 per cent was related to disease progression rather than the procedure. Endoscopic stent insertion may achieve further worthwhile palliation of jaundice after the failure of surgery to relieve malignant biliary obstruction.

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.

Amoxycillin/clavulanic acid (Augmentin)-induced intrahepatic cholestasis.

A 75-year-old man developed a biopsy-proven, drug-induced intrahepatic cholestasis after use of amoxycillin trihydrate combined with the beta-lactam inhibitor potassium clavulanate (Augmentin). Cholestatic liver injury is an uncommonly recognized, probably immunologically based adverse reaction to therapy with penicillin and its derivatives.

Small bowel dysmotility in patients with postcholecystectomy sphincter of Oddi dysfunction.

Postcholecystectomy patients (N = 27) with severe recurrent biliary-like pain who had no evidence of organic disease were subdivided into those with and those without objective evidence of sphincter of Oddi dysfunction (SOD) based on two separate criteria: (1) clinical criteria-elevated liver function tests and/or amylase with pain, and/or a dilated bile duct, and/or delayed drainage at ERCP (N = 14, SOD classes I and II); and (2) abnormal biliary manometry (N = 19). Prolonged (24-48 hr) ambulant recording of duodenojejunal motor activity was performed in all patients and interdigestive small bowel motor activity compared between patient subgroups and a healthy control group. Phase II motor abnormality was more frequent in patients with, compared to those without, objective clinical criteria of SOD (7/14 vs 0/13, P = 0.003). Phase III abnormality also tended to be more frequent in these patients (7/14 vs 2/13, P = 0.06). In addition, both phase III (P = 0.03) and phase II (P = 0.03) motility index (MI) was higher in patients with sphincter dyskinesia compared to controls; phase II MI was also higher in patients with sphincter stenosis (P = 0.005). Disturbances of small bowel interdigestive motor activity are more prevalent in postcholecystectomy patients with, compared to those without, objective evidence of SOD, and especially in patients with SO dyskinesia. Postcholecystectomy SOD in some patients may thus represent a component of a more generalized intestinal motor disorder.

Discordance of pressure recordings from biliary and pancreatic duct segments in patients with suspected sphincter of Oddi dysfunction.

It remains controversial whether manometric parameters recorded from the pancreatic and biliary segment of the sphincter of Oddi (SO) differ. We therefore studied 48 consecutive patients (40 women, 43 +/- 11 years) with suspected SO dysfunction, in 33 of whom successful dual-duct SO manometry was obtained. Measures of concordance between the two duct segments were moderate for basal sphincter pressure (K = 0.31) and for contractile frequency (0.35), and were low for peak pressure (0.15) and for proportion of retrograde propagation (-0.19). There was also low concordance (-0.13) for the overall manometric diagnosis, and in 48% (CI 31-66%) of patients a conflicting diagnosis (normal/abnormal) was obtained from the two ducts. There was no evidence of a differential motor effect of CCK on either duct, nor were there significant differences in the rate of manometric abnormality according to the order of initial duct cannulation. These results indicate that, if technically feasible, dual-duct manometry of the sphincter of Oddi is required for diagnostic precision.

Abnormal sphincter of Oddi response to cholecystokinin in postcholecystectomy syndrome patients with irritable bowel syndrome. The irritable sphincter.

Standard biliary manometry, including cholecystokinin (CCK) provocation, was performed on 42 consecutive patients (36 F, 6 M, median age 45 years) with postcholecystectomy syndrome (PCS) who had no evidence of organic disease but who had objective clinical features suggesting sphincter of Oddi dysfunction (SOD) (classes I and II). Patients were subdivided into those with (N = 14) and without (N = 28) irritable bowel syndrome (IBS) using a validated symptom questionnaire based on the modified Rome criteria. Resting sphincter of Oddi (SO) motor parameters (basal pressure, contractile amplitude and frequency, and proportion of retrograde contractions), the presence of abnormal manometry, and the presence of an abnormal response to CCK were compared in the two groups. No significant differences in resting parameters of SO motor activity between patients with and without IBS were observed, and abnormal biliary manometry as a whole was not more prevalent in either group (8/13 and 18/27, respectively). An abnormal response to CCK (failure of complete inhibition of phasic contractions), however, was demonstrated in five of 12 patients with IBS compared with only one of 23 patients without IBS (P = 0.01). In patients with postcholecystectomy SOD, an abnormal response of the SO to CCK thus appears to be an important feature of the subset of patients with concomitant IBS.

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.

A comparison of right versus left hepatic duct endoprosthesis insertion in malignant hilar biliary obstruction.

Endoscopic endoprosthesis insertion plays an increasingly important role in the palliation of jaundice in patients with unresectable malignant hilar biliary obstruction (HBO). Drainage of both obstructed lobes in Types II and III HBO is not necessary to achieve adequate palliation, providing 25% of the liver volume is drained by a single endoprosthesis. The anatomy of the main hepatic ducts suggests some benefit may accrue from preferential drainage of the left hepatic duct. We have reviewed a consecutive series of 151 patients with Type II and III HBO over a 4-year period to compare the outcome of endoprosthesis placement in either the right (RHD) or left (LHD) hepatic duct, to test this hypothesis. No significant difference was found in terms of successful drainage, complications, 30-day mortality, number of endoprosthesis changes and survival between patients with right system drainage compared with those with left sided drainage (chi 2-test and Mann Whitney U test). When dealing with a patient with a Type II or III HBO, we would recommend single endoscopic endoprosthesis insertion into the technically most accessible obstructed system. This would achieve adequate palliation in 84% of the patients.

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.

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.