Routine pre- and post-neoadjuvant chemotherapy fitness testing is not indicated for oesophagogastric cancer surgery.

Introduction There is a known correlation between anaerobic threshold (AT) during cardiopulmonary exercise testing and development of cardiopulmonary complications in high-risk patients undergoing oesophagogastric cancer surgery. This study aimed to assess the value of routine retesting following neoadjuvant chemotherapy. Methods Patients undergoing neoadjuvant chemotherapy with subsequent oesophagogastric cancer surgery with pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise data were identified from a prospectively maintained database. Measured cardiopulmonary exercise variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Anaerobic threshold values within 1 ml/kg/minute were considered static. Patients were grouped into AT ranges of less than 9 ml/kg/minute, 9-11 ml/kg/minute and greater than 11 ml/kg/minute. Outcome measures were unplanned intensive care stay, postoperative cardiovascular morbidity and mortality. Results Between May 2008 and August 2017, 42 patients from 675 total resections were identified, with a mean age of 65 years (range 49-84 years). Mean pre-neoadjuvant chemotherapy AT was 11.07 ml/kg/minute (standard deviation, SD, 3.24 ml/kg/minute, range 4.6-19.3 ml/kg/minute) while post-neoadjuvant chemotherapy AT was 11.19 ml/kg/minute (SD 3.05 ml/kg/minute, range 5.2-18.1 ml/kg/minute). Mean pre-neoadjuvant chemotherapy VO2 peak was 17.13 ml/kg/minute, while post-chemotherapy this mean fell to 16.59 ml/kg/minute. Some 44.4% of patients with a pre-chemotherapy AT less than 9 ml/kg/minute developed cardiorespiratory complications compared with 42.2% of those whose AT was greater than 9 ml/kg/minute (P = 0.914); 63.6% of patients in the post-neoadjuvant chemotherapy group with an AT less than 9 ml/kg/minute developed cardiorespiratory complications. There was no correlation between direction of change in AT and outcome. Conclusion In our patient population, neoadjuvant chemotherapy does not appear to result in a significant mean reduction in cardiorespiratory fitness. Routine pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise testing is currently not indicated; however, larger studies are required to demonstrate this conclusively.

Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett's oesophagus.

BACKGROUND: Barrett's high grade dysplasia (HGD) is a pre-malignant condition which requires treatment with either oesophagectomy or ablative endoscopic therapy. Endoscopic ablative techniques have evolved through Photodynamic Therapy (PDT) to more recently radiofrequency ablation (RFA). Although RFA has superseded PDT due to improved efficacy and safety profile there remains a significant cohort of patients previously treated by PDT where the long term outcome is unclear. This study's aim was to assess the long term efficacy of PDT in patients with Barrett's HGD. METHODS: Between June 2002 and 2007 21 patients (16 male, median age 70) underwent PDT for HGD in Barrett's oesophagus. Patients received intravenous photosensitiser Photofrin (Porfimer sodium) forty eight hours prior to endoscopic light activation by laser light at 630 nm. The patients returned at 6-12 weekly intervals for repeat endoscopy and biopsy. RESULTS: Sixteen patients remained free of HGD at median 62 (range 36-114) months. Three patients developed adenocarcinoma at 47, 48 and 54 months (15%). Two patients were treated endoscopically with RFA and YAG laser, while one patient had surgical resection. Four patients developed recurrent HGD treated with repeat PDT. There was a significant reduction in length of Barrett's segment (from 5 cm to 3 cm) post PDT. The stricture rate requiring endoscopic therapy was 37% and 10% of patients developed photosensitivity reactions. CONCLUSION: PDT successfully ablated HGD in 84% of patients and could therefore still be considered an effective salvage treatment for this condition in patients with co-morbidities precluding them for surgical resection.

Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery.

INTRODUCTION: An anaerobic threshold (AT) of <11 ml/min/kg can identify patients at high risk of cardiopulmonary complications after major surgery. The aim of this study was to assess the value of cardiopulmonary exercise testing (CPET) in predicting cardiopulmonary complications in high risk patients undergoing oesophagogastric cancer resection. METHODS: Between March 2008 and October 2010, 108 patients (83 men, 25 women) with a median age of 66 years (range: 38-84 years) underwent CPET before potentially curative resections for oesophagogastric cancers. Measured CPET variables included AT and maximum oxygen uptake at peak exercise (VO2 peak). Outcome measures were length of high dependency unit stay, length of hospital stay, unplanned intensive care unit (ICU) admission, and postoperative morbidity and mortality. RESULTS: The mean AT and VO2 peak were 10.8 ml/min/kg (standard deviation [SD]: 2.8 ml/min/kg, range: 4.6-19.3 ml/min/kg) and 15.2 ml/min/kg (SD: 5.3 ml/min/kg, range: 5.4-33.3 ml/min/kg) respectively; 57 patients (55%) had an AT of <11 ml/min/kg and 26 (12%) had an AT of <9 ml/min/kg. Postoperative complications occurred in 57 patients (29 cardiopulmonary [28%] and 28 non-cardiopulmonary [27%]). Four patients (4%) died in hospital and 21 (20%) required an unplanned ICU admission. Cardiopulmonary complications occurred in 42% of patients with an AT of <9 ml/min/kg compared with 29% of patients with an AT of ≥9 ml/min/kg but <11 ml/min/kg and 20% of patients with an AT of ≥11 ml/min/kg (p = 0.04). There was a trend that those with an AT of <11 ml/min/kg and a low VO2 peak had a higher rate of unplanned ICU admission. CONCLUSIONS: This study has shown a correlation between AT and the development of cardiopulmonary complications although the discriminatory ability was low.

The relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.

BACKGROUND: There is increasing evidence that the local and systemic inflammatory responses are associated with survival in oesophageal cancer. The aim of this study was to examine the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation and microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma. METHODS: The interrelationship between tumour necrosis, tumour proliferation, local inflammatory response (Klintrup-Makinen criteria, intra-tumoural CD8+ lymphocyte and macrophage infiltration), systemic inflammatory response (modified Glasgow Prognostic score (mGPS)), and microvessel density was examined in 121 patients undergoing potentially curative resection for oesophageal adenocarcinoma (including type I and II tumours of the gastro-oesophageal junction). RESULTS: Tumour necrosis was not significantly associated with any tumour measure other than the degree of differentiation. On multivariate analysis, only age (HR 1.93, 95% CI 1.23-3.04, P=0.004), mGPS (HR 2.91, 95% CI 1.51-5.62, P=0.001), positive to total lymph node ratio (HR 2.38, 95% CI 1.60-3.52, P<0.001) and macrophage infiltration (HR 1.49, 95% CI 1.02-2.18, P=0.041) were independently associated with cancer-specific survival in oesophageal adenocarcinoma. Intra-tumoural macrophages were associated with tumour proliferation (P<0.001) and CD8+ lymphocytes infiltration (P<0.01). CONCLUSION: The results of this study suggest that tumour necrosis does not link local and systemic inflammatory responses and is not significantly associated with survival. In contrast, tumour macrophage infiltration appears to have a central role in the proliferative activity and the coordination of the inflammatory cell infiltrate and is independently associated with poorer survival in patients with oesophageal adenocarcinoma.

Randomized clinical trial comparing self-expanding metallic stents with plastic endoprostheses in the palliation of oesophageal cancer.

BACKGROUND: There is little evidence of the clinical and cost effectiveness of self-expanding metallic stents in the palliation of oesophageal cancer. The aims of this randomized trial were to evaluate the immediate and medium-term clinical outcomes following palliative intubation, examine patient quality of life, and evaluate costs and benefits from the perspective of the health service. METHODS: Fifty patients with inoperable oesophageal cancer were randomly allocated a metallic stent (n = 25) or plastic endoprosthesis (n = 25). Patients were followed up monthly until death. RESULTS: There was no significant difference in procedure-related complications or mortality rate between the two groups. There was a trend towards significance in favour of metallic stents with respect to quality of life and survival (median survival 62 versus 107 days for plastic prosthesis and metallic stent respectively). The cost of the initial placement of metallic stents was significantly higher than that of plastic endoprostheses ( pound 983 versus pound 296). After 4 weeks, cost differences were no longer significant. CONCLUSION: Metallic stents may contribute to improved survival and quality of life in patients with oesophageal cancer. Although initially more expensive, this cost difference does not last beyond 4 weeks. A larger trial involving approximately 300 patients would be required to detect a quality of life benefit of the magnitude observed in this trial.

A phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma.

BACKGROUND: The purpose of this study was to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose of capecitabine when used in combination with epirubicin and cisplatin (ECC) in patients with oesophageal or gastric adenocarcinoma. Response rate, progression-free survival (PFS) and overall survival were also determined, and the effect of previous oesophago-gastric surgery or concurrent oesophago-gastric cancer on the absorption and metabolism of capecitabine was evaluated. PATIENTS AND METHODS: Patients with inoperable oesophago-gastric adenocarcinoma received up to six cycles of epirubicin (50 mg/m(2) i.v., 3-weekly), cisplatin (60 mg/m(2) i.v., 3-weekly) and capecitabine, the latter administered orally in an intermittent schedule (14 days treatment; 7-day rest period) at 3-weekly intervals. Patients were recruited into one of four escalating dose cohorts (500, 825, 1000 and 1250 mg/m(2) bd). Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level, with DLT assessed on the toxicity of the first cycle only. Blood sampling for pharmacokinetic analyses was performed over the first 10 h of day 1 of cycle 1. RESULTS: Thirty-two patients, median age 63 years (range 32-76 years), ECOG performance status < or =2 with locally advanced (10) or metastatic (22) disease were recruited and were evaluable for toxicity. Two of five patients experienced DLT at 1250 mg/m(2) bd with grade II stomatitis (one patient) and grade III diarrhoea with febrile neutropenia (one patient). Cumulative toxicity for all cycles (n = 140) (worst grade per patient) includes grade IV oesophagitis (one patient), grade III diarrhoea (five), grade IV neutropenia with infection (seven), grade II stomatitis (four) and grade IV thrombocytopenia (one). Of 29 patients with evaluable disease, there was one complete response and six partial responses [24% response rate [95% confidence interval (CI) 10% to 44%]], a median PFS of 22 weeks (95% CI 17-27 weeks) and median overall survival of 34 weeks (95% CI 19-49 weeks). Capecitabine was rapidly absorbed after oral administration, with a t(max) of 1-2 h for capecitabine, DFCR (5'-deoxy-5-fluorocytidine) and DFUR (5'-deoxy-5-fluorouridine). The C(max) and AUC(0-)( infinity ) for capecitabine, DFCR and DFUR were similar to those observed in previous monotherapy studies of capecitabine taken after food. CONCLUSION: A dose of 1000 mg/m(2) bd of capecitabine is recommended for use on an intermittent schedule in combination with these doses and schedule of epirubicin and cisplatin. This regimen is tolerable and active in oesophago-gastric adenocarcinoma. A randomised phase III comparison with ECF is justified.

A phase II study of epirubicin, cisplatin and raltitrexed combination chemotherapy (ECT) in patients with advanced oesophageal and gastric adenocarcinoma.

BACKGROUND: The aim of this study was to evaluate the efficacy of the combination of epirubicin, cisplatin and ralitrexed (Tomudex). ECT, in patients with advanced oesophageal or gastric adenocarcinoma. Efficacy was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Twenty-one patients with histologically and/or cytologically proven unresectable (7) or metastatic (14) gastro-oesophageal adenocarcinoma, who had bi-dimensionally measurable disease, with ECOG performance status < or = 2. with adequate haematological, hepatic and renal function received first-line chemotherapy with epirubicin (50 mg/m2). cisplatin (60 mg/m2) and Tomudex (2.5 mg/m2), ECT, at three-weekly intervals. Treatment consisted of three cycles of chemotherapy, with a further three cycles if there was disease response or stabilisation. RESULTS: ECT is an active regimen in the treatment of advanced gastro-oesophageal adenocarcinoma with an overall intention-to-treat response rate of 29% (95% confidence intervals (CI): 11%-52%). In addition, 4 (19%) patients had stable disease. Median time to progression was 19 weeks (95% CI: 7-31 weeks). Median overall survival was 18 weeks (95% CI: 11-24 weeks). Seventeen patients failed to complete the six cycles of treatment due to disease progression (5). toxicity (3), non-toxic death (1 pulmonary embolism, 1 cardiac), severe allergy to epirubicin (1), patient decision (1) and five patients after the study was discontinued early due to toxicity. There were three toxic deaths: two due to sepsis complicating neutropaenia and one due to cardiorespiratory failure following drug induced enteritis. Nine patients experienced grade 3 or 4 neutropaenia, two patients experienced grade 3 or 4 nausea and vomiting and one patient had grade 4 diarrhoea. CONCLUSIONS: The combination of epirubicin, cisplatin and tomudex is active against advanced gastro-oesophageal adenocarcinoma but the toxicity suggests that further evaluation in a randomised comparison to ECF is not appropriate.

Incidence and nature of bile duct injuries following laparoscopic cholecystectomy: an audit of 5913 cases. West of Scotland Laparoscopic Cholecystectomy Audit Group.

The rapid introduction of laparoscopic cholecystectomy has been associated with an apparently increased incidence of bile duct injury which has provoked worldwide concern. The true incidence and mechanism of iatrogenic ductal injury during the development of this procedure remain unclear. To assess this, the introduction of laparoscopic cholecystectomy in the West of Scotland has been audited prospectively over a 5-year period. All cases of biliary ductal injury have been independently reviewed. Some 48 surgeons undertaking laparoscopic cholecystectomy in 19 hospitals submitted prospective data between September 1990 and September 1995. A total of 5913 laparoscopic cholecystectomies were attempted with 98.3 per cent completion of data collection. During this period 37 laparoscopic bile duct injuries occurred. The annual incidence peaked at 0.8 per cent and has fallen to 0.4 per cent in the final year of audit. Injuries occurred after a median personal experience of 51 (range 3-247) laparoscopic cholecystectomies in 22 surgeons. Major bile duct injuries occurred in 20 of 37 patients, giving an incidence of 0.3 per cent. Five mechanisms for laparoscopic ductal injury were identified, including tenting, confluence and diathermy injuries as well as the classical and variant classical types. Ductal injuries were discovered at operation in 18 patients with consequent repair giving a good clinical outcome in 17. Contributory factors (severe inflammation, aberrant anatomy and poor visualization) were present in only 13 of 37 cases. This audit suggests that, at least in the introductory period, laparoscopic cholecystectomy is associated with an overall bile duct injury rate higher than that reported previously after open cholecystectomy, although the incidence of major ductal injury is similar. The late downward trend in bile duct injury, however, suggests there may be a prolonged learning curve for this procedure. Improved understanding of the mechanism of injury may lead to yet further reductions in this complication.

Early outcome after open versus extraperitoneal endoscopic tension-free hernioplasty: a randomized clinical trial.

BACKGROUND: The use of minimal access surgery for repair of groin hernias is controversial. The aim of this study was to compare endoscopic tension-free hernia repair with open tension-free hernia repair within a randomized clinical trial. METHODS: One hundred twenty patients were randomized by four surgeons during a 1-year period. Early outcome measures were then analyzed by intention to treat. RESULTS: Median postoperative pain scores (63 [interquartile range (IQR), 23 to 81] versus 35 [IQR, 17 to 62]; p = 0.004) and analgesia requirements (2.5 [IQR, 2 to 4] doses verus 2.0 [IQR, 1 to 3] doses; p = 0.0008) were significantly less for patients undergoing endoscopic hernia repair. Hospital stay (1 [IQR, 0 to 1] day versus 2 [IQR, 1 to 2] days; p < 0.0001) was also significantly reduced for the endoscopic group. Wound complications occurred significantly more frequently in the open group. No difference in pulmonary function or metabolic response to trauma (interleukin-6, C-reactive protein, glucose, albumin) was observed between the groups. CONCLUSIONS: This study shows significant short-term advantages for endoscopic tension-free repair over open tension-free repair. However, larger studies with a longer follow-up period are required to establish the relative merits of both procedures in the management of patients with groin hernias.

Prospective audit of the introduction of laparoscopic cholecystectomy in the west of Scotland. West of Scotland Laparoscopic Cholecystectomy Audit Group.

Although laparoscopic cholecystectomy has rapidly developed in the treatment of gall bladder disease in the absence of controlled clinical trial data its outcome parameters compared with open cholecystectomy remain unclear. A prospective audit of the introduction of laparoscopic cholecystectomy in the west of Scotland over a two year period was carried out to attempt to assess this new procedure. A total of 45 surgeons in 19 hospitals performing laparoscopic cholecystectomy submitted prospective data from September 1990-1992. A total of 2285 cholecystectomies were audited (a completed data collection rate of 99%). Laparoscopic cholecystectomy was attempted in 1683 (74%) patients and completed in 1448 patients (median conversion rate to the open procedure 17%). The median operation time in the completed laparoscopic cholecystectomy patients was 100 minutes (range 30-330) and overall hospital stay three days (1-33). There were nine deaths (0.5%) after laparoscopic cholecystectomy although only two were directly attributable to the laparoscopic procedure. In the laparoscopic cholecystectomy group there were 99 complications (5.9%), 53 (3%) of these were major requiring further invasive intervention. Forty patients (2.4%) required early or delayed laparotomy for major complications such as bleeding or bile duct injuries. There were 11 (0.7%) bile duct injuries in the laparoscopic cholecystectomy series, five were noted during the initial procedure and six were recognised later resulting from jaundice or bile leaks. Ductal injuries occurred after a median of 20 laparoscopic cholecystectomies. In conclusion laparoscopic cholecystectomy has rapidly replaced open cholecystectomy in the treatment of gall bladder disease. Although the overall death and complication rate associated with laparoscopic cholecystectomy is similar to open cholecystectomy, the bile duct injury rate is higher.

Evaluation of the cost of laparoscopic and open cholecystectomy.

Despite the rapid growth of laparoscopic cholecystectomy, the comparative costs of this new procedure and open cholecystectomy remain unknown. In this study the costs have been evaluated of a consecutive series of patients undergoing these procedures in a district general hospital with an established resource management centre. Fifty consecutive patients undergoing open cholecystectomy between June 1988 and July 1990 immediately before the introduction of laparoscopic cholecystectomy and 100 patients undergoing laparoscopic cholecystectomy between August 1990 and June 1992 were studied. Costs estimated prospectively for each patient were compared. The mean cost per patient of open cholecystectomy was estimated at 2102 pounds compared with 2026 pounds for the first 50 patients undergoing the laparoscopic procedure. The mean cost (1744 pounds) for the second 50 patients undergoing laparoscopic cholecystectomy was less than that for either open cholecystectomy (P < 0.005) or the initial 50 laparoscopic operations (P < 0.03). Operating theatre costs and equipment costs were higher in both laparoscopic groups. These were offset by the higher nursing and ward costs of open cholecystectomy. For the laparoscopic procedure the operating theatre times and duration of hospital stay were both less in the second 50 patients than in the first 50. After the initial learning period, laparoscopic cholecystectomy is less expensive than the open operation and represents a cost-effective method for treatment of the patient with gallstones.

Helicobacter pylori related hypergastrinaemia is the result of a selective increase in gastrin 17.

Helicobacter pylori infection increases the serum concentration of gastrin, and this may be one of the mechanisms by which it predisposes to duodenal ulceration. Different forms of circulating gastrin were studied both basally and postprandially in 13 duodenal ulcer patients before and one month after eradication of H pylori. Three antisera that are specific for particular regions of the gastrin molecules were used. Gel chromatography indicated that > 90% of the circulating gastrin consisted of gastrin (G) 17 and G34 both before and after eradicating the infection. The basal median total immunoreactive gastrin concentration fell from 26 pmol/l (range 11-43) to 19 pmol/l (8-39) (p < 0.05), entirely because of a fall in G17 from 6 pmol/l (< 2.4-25) to < 2.4 pmol/l (< 2.4-23) (p < 0.001). The median (range) basal G34 values were similar before (15 pmol (2-36)) and after (10 pmol (2-30)) eradication. The median total immunoreactive gastrin concentration determined 20 minutes postprandially fell from 59 pmol/l (38-114) to 33 pmol/l (19-88) (p < 0.005), and again this was entirely the result of a fall in G17 from 43 pmol/l (9-95) to 17 pmol/l (< 2.4-52) (p < 0.001). The median postprandial G34 values were similar before (13 pmol/l, range 6-42) and after (15 pmol/l, range 6-30) eradication. Eating stimulated a noticeable rise in G17 but little change in G34, both in the presence and absence of H pylori. The finding that H pylori infection selectively increases G17 explains why the infection causes mainly postprandial hypergastrinaemia. G17 is increased selectively because H pylori predominantly affects the antral mucosa which is the main source of G17 whereas G34 is mainly duodenal in origin. This study also indicates that the increased concentration of gastrin in H pylori infection is the result of an increase in one of the main biologically active forms of the hormone.

The effect of H2-blockade on plasma gastrin concentration in patients with an achlorhydric stomach.

The mechanisms of hypergastrinaemia during H2-receptor antagonist therapy remain unclear. In addition, the effect of food stimulation in conditions of hypergastrinaemia is poorly understood. These effects may be important when considering long-term therapy with potent acid inhibitory agents. To investigate this we studied the effect of H2-receptor antagonist therapy on basal and meal-stimulated plasma gastrin concentrations in 9 patients with pentagastrin fast gastric achlorhydria associated with pernicious anaemia. The subjects received in double-blind randomized fashion 28-day courses of 300 mg ranitidine q.d.s. and placebo, with one-month wash-out between. The fasting and peptone meal-stimulated gastrin concentrations were studied on the final day of each course of treatment. The median fasting gastrin concentrations (ng/L) were similar following placebo (1100, range 25-2100), and 300 mg ranitidine q.d.s. (1075, range 15-2600) and both markedly elevated when compared with our laboratory's normal range of 0-100. Despite the elevated basal levels the pernicious anaemia patients still showed a further increase in response to the peptone meal. Their median peak percentage rise over basal in response to the meal was similar following placebo (96%, range 0-375) and 300 mg ranitidine q.d.s. (100%, range 25-425) (both P less than 0.02 c.f. basal). This study shows that: (a) in hypergastrinaemia in pernicious anaemia subjects, meal stimulation leads to a marked and prolonged increase in plasma gastrin concentrations; (b) H2-receptor antagonists have no effect on plasma gastrin in the neutral stomach and this is consistent with their gastrin effect being entirely secondary to acid inhibition.

Controlled study of the effect of nicardipine and ceruletide on the sphincter of Oddi.

Although sphincter of Oddi dysfunction is a recognised cause of post cholecystectomy pain, the control mechanisms involved in sphincter of Oddi function are poorly understood. Pharmacological relaxation of the sphincter of Oddi may have a beneficial effect particularly in sphincter of Oddi dysfunction where basal sphincter pressure is high. The aim of this study was to investigate the effects of calcium channel blockade (nicardipine) and synthetic cholecystokinin (ceruletide) on sphincter of Oddi pressures. Nineteen patients (median age 49 years; range 21-75) attending for routine endoscopic retrograde cholangiopancreatographic (ERCP) examination were studied. No patients with evidence of sphincter of Oddi dysfunction were included in the study. Each patient was randomly allocated to receive a three minute intravenous infusion of nicardipine 3 mg (six) ceruletide 5 ng/kg (seven) or placebo (six). Endoscopic biliary manometry was done with recording of basal sphincter of Oddi pressures, sphincter of Oddi phasic wave amplitude and frequency before and after intravenous infusions. In the nicardipine group patients showed a decrease in both basal and phasic amplitude sphincter of Oddi pressure (mm Hg) from the preinfusion values (mean (SEM)) of 24.7 (3.6) and 112.3 (13.4) to 12.9 (2.9) (p less than 0.01) and 89.9 (12.4) (p less than 0.03) after infusion respectively. Ceruletide produced a decrease in sphincter of Oddi phasic wave frequency (c/min) from 3.4 (0.3) before infusion to 2.6 (0.5) after infusion (p less than 0.05). We conclude that nicardipine effectively decreases sphincter of Oddi pressure. This drug may therefore be of value in the treatment of sphincter of Oddi dysfunction where raised sphincter pressures are thought to be the primary pathogenic feature.

Evaluation of endoscopic sphincterotomy in sphincter of Oddi dysfunction.

In this prospective study the efficacy of endoscopic sphincterotomy was evaluated in ten post-cholecystectomy patients with clinical and biliary manometric evidence of SO dysfunction. Ten patients (8 females, 2 males, median age 59 years) were assessed at a median period of 24 months (range 12-48) after endoscopic sphincterotomy. Eight of the ten patients (80%) were symptomatically improved after endoscopic sphincterotomy although only four were totally asymptomatic. The two patients who had unchanged symptoms after sphincterotomy have since had alternative diagnoses made and have improved on appropriate therapy. It is concluded that endoscopic sphincterotomy is effective in relieving symptoms in post-cholecystectomy patients with clinical and manometric evidence of SO dysfunction.

Helicobacter pylori and hypergastrinaemia during proton pump inhibitor therapy.

The rise in serum gastrin and pepsinogen I after 5 days' treatment with the proton pump inhibitor pantoprazole (40 mg/day) was examined in eight duodenal ulcer patients with Helicobacter pylori infection and compared with eight in whom it had been eradicated. Before treatment, the post-prandial serum gastrin concentrations were higher in the H. pylori-positive than -eradicated patients (p less than 0.05). The median rise in pre-prandial serum gastrin concentrations on treatment was similar in the H. pylori-positive (41%) and -eradicated patients (45%). The rise in post-prandial serum gastrin was also similar in the H. pylori-positive (81%) and -eradicated patients (69%), resulting in significantly higher gastrin concentrations during treatment in the former. The median rise in serum pepsinogen I on treatment was greater in the H. pylori-positive (114%) than in the -eradicated patients (8%), resulting in significantly higher concentrations during treatment in the former. These observations indicate that eradication of H. pylori may be a means of moderating the hypergastrinaemia caused by acid-inhibitory therapy. They also indicate that H. pylori-related hypergastrinaemia is not due to an increase of the antral surface pH by the bacterium's urease activity.

Gallbladder and pancreatic metastases from bilateral renal carcinoma presenting with hematobilia and anemia.

A case of bilateral metachronous renal cell carcinoma with gallbladder and pancreatic metastases, presenting with hematobilia and anemia is presented. The presentation of metastatic renal cell carcinoma with hematobilia and anemia is previously unreported. This case illustrates (1) the occasionally very long interval between metachronous renal carcinoma; (2) this tumor's propensity to unusual metastases and unpredictable presentation; and (3) the significant palliation which may be achieved by appropriate surgical resection of these metastases.

Rebound hypersecretion after H2-antagonist withdrawal--a comparative study with nizatidine, ranitidine and famotidine.

Our previous study demonstrated rebound nocturnal acid hypersecretion after a 4-week course of nizatidine. Nocturnal acid output was increased by 77% two days after discontinuing treatment compared with pretreatment values. To confirm this effect with other H2-blockers we assessed daytime intragastric pH, fasting and meal-stimulated plasma gastrin and nocturnal acid output in 9 duodenal ulcer patients in remission before, during and two days after treatment with three different drugs. Each patient received 4-week courses of 300 mg ranitidine, 40 mg famotidine or 300 mg nizatidine, taken at 20.00 hours in randomized order with a 'washout' period of 4 weeks between each course of drug. Median nocturnal acid output (mmol/10 h) decreased during treatment with ranitidine to 3 (range 0-17), famotidine to 4 (1-12) and nizatidine 6 (0-40) compared with the respective pre-treatment values, 49 (20-126; P less than 0.01), 52 (22-105; P less than 0.01) and 32 (23-114; P less than 0.01). Two days after discontinuing treatment nocturnal acid output was increased after ranitidine at 77 (28-237; P less than 0.04) and after nizatidine at 64 (17-130; P less than 0.05) compared with pre-treatment values. There was no significant change in nocturnal acid output after famotidine at 57 (27-107) compared with the pre-treatment value. There was no change in daytime intragastric pH with any drug during or after treatment compared with the pre-treatment values. Fasting and meal-stimulated plasma gastrin concentrations were increased on the final treatment day with ranitidine and famotidine but had returned to pretreatment levels two days after treatment. The rebound acid hypersecretion may contribute to the high ulcer relapse rate after discontinuation of H2-receptor antagonists.