Endoscopic Botulinum toxin as a treatment for delayed gastric emptying following oesophagogastrectomy.

INTRODUCTION: The incidence of delayed gastric emptying (DGE) following oesophagogastrectomy with gastric conduit reconstruction is reported to be between 1.7% and 50%. This variation is due to differing practices of intraoperative pylorus drainage procedures, which increase the risk of postoperative biliary reflux and dumping syndrome, resulting in significant morbidity. The aim of our study was to establish rates of DGE in people undergoing oesophagogastrectomy without routine intraoperative drainage procedures, and to evaluate outcomes of postoperative endoscopically administered Botulinum toxin into the pylorus (EBP) for people with DGE resistant to systemic pharmacological treatment. METHODS: All patients undergoing oesophagogastrectomy between 1 January 2016 and 31 March 2018 at our unit were included. No intraoperative pyloric drainage procedures were performed, and DGE resistant to systemic pharmacotherapy was managed with EBP. RESULTS: Ninety-seven patients were included. Postoperatively, 29 patients (30%) were diagnosed with DGE resistant to pharmacotherapy. Of these, 16 (16.5%) were diagnosed within 30 days of surgery. The median pre-procedure nasogastric tube aspirate was 780ml; following EBP, this fell to 125ml (p<0.001). Median delay from surgery to EBP in this cohort was 13 days (IQR 7-16 days). Six patients required a second course of EBP, with 100% successful resolution of DGE before discharge. There were no procedural complications. CONCLUSIONS: This is the largest series of patients without routine intraoperative drainage procedures. Only 30% of patients developed DGE resistant to pharmacotherapy, which was managed safely with EBP in the postoperative period, thus minimising the risk of biliary reflux in people who would otherwise be at risk following prophylactic pylorus drainage procedures.

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.

BACKGROUND: Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. METHODS: We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008-2010 and 2011-2013). Durability of successful treatment and progression to OAC were also evaluated. RESULTS: 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). CONCLUSIONS: Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2-4% at 1 year in these high-risk patients. TRIAL REGISTRATION NUMBER: ISRCTN93069556.

When is pancreatitis considered to be of biliary origin and what are the implications for management?

Acute pancreatitis is a disease caused by gallstones in 40-60% of patients. Identification of these patients is extremely important, since there are specific therapeutic interventions by endoscopic sphincterotomy and/or cholecystectomy. The combination of trans-abdominal ultrasound (stones in the gallbladder and/or main bile duct) and elevated serum alanine transaminase (circa >60 IU/l within 48 h of presentation) indicates gallstones as the cause in the majority of patients with acute pancreatitis. In the presence of a severe attack this is a strong indication for intervention by endoscopic sphincterotomy. The presence of a significant main bile duct dilatation is also strongly indicative of gallstones and should prompt the use of endoluminal ultrasonography: >8 mm diameter with gallbladder in situ, or >10 mm following cholecystectomy if aged <70 years and >12 mm, respectively, if > or = 70 years. In mild pancreatitis surgically fit patients should be treated by cholecystectomy, and intra-operative cholangiography, as pre-operative biliary imaging is not efficient in this setting. Patients who are not fit for cholecystectomy should undergo prophylactic endoscopic sphincterotomy to prevent further attacks. In the post-acute-phase, pancreatitis patients in whom the aetiology is uncertain should undergo endoluminal ultrasonography. Thisis the most sensitive method for the detection of cholelithiasis and choledocholithiasis and may reveal alternative aetiological factors such as a small ampullary or pancreatic cancer. A number of recent studies have shown that bile crystal analysis, a marker for microlithiasis, increases the yield of positive results over and above endoluminal ultrasonography, and should be considered as part of the modern investigative algorithm.

TIPSS in the treatment of ectopic variceal bleeding.

BACKGROUND/AIMS: Bleeding from ectopic varices is a well recognized life-threatening complication of portal hypertension but the optimal treatment of this problem is yet to be established. METHODOLOGY: We retrospectively reviewed patients with ectopic variceal bleeding who underwent transjugular intrahepatic portosystemic shunting for recurrent bleeding not responding to conservative management. RESULTS: Over an eleven-year period we identified ten patients who underwent TIPSS for ectopic variceal hemorrhage. Six patients bled from rectal varices and four from stomal varices. TIPSS was successful in nine patients. The Childs-Pugh grade of the patients was A=3, B=3 and C=4. The follow-up period ranged from 7 days to 1380 days. Rebleeding occurred in three patients, two of whom died. The remaining patient had a blocked TIPSS and successfully underwent repeat stenting which re-established patency. Four patients (Childs B=2, Childs C=2) died within 60 days. All three patients with Childs A liver disease were alive at one year. CONCLUSIONS: TIPSS can be used effectively to treat ectopic variceal bleeding. Patients with Childs grade A liver disease appear to do well with TIPSS. Those with advanced liver disease (Childs B & C) have a uniformly poor outcome. In these patients ectopic variceal hemorrhage is likely to represent a terminal event.

T cell lymphoplasmacellular and eosinophilic infiltration of the pancreas with involvement of the gallbladder and duodenum in non-alcoholic duct-destructive chronic pancreatitis.

BACKGROUND: Non-alcoholic duct destructive chronic pancreatitis is a rare entity with specific pathological features. The majority of the patients are from Japan. We report a case with involvement of the distal bile duct, the gallbladder, the duodenum and the ampulla, and present a review of patients from Europe and the USA since 1997. CASE PRESENTATION: A 56-year-old man presented with a 3-month history of mild acute pancreatitis and obstructive jaundice, followed by increasing weight loss, lethargy and epigastric pain. CT showed a mass in the head of the pancreas. ERCP demonstrated a smooth stricture of the intra-pancreatic main bile duct and an irregular, incomplete, stricture in the main pancreatic duct. A pancreatic cancer could not be reliably excluded, and, therefore, he underwent a pylorus-preserving Kausch-Whipple's pancreatoduodenectomy. RESULTS: Histopathology showed typical peri-ductal T cell-rich lymphoplasmacellular and eosinophilic infiltration of the pancreas, with involvement of the distal bile duct but, also, unusual inflammatory infiltration of the gallbladder, the duodenum and the ampulla. CONCLUSION: The inflammatory process in non-alcoholic duct-destructive chronic pancreatitis can affect the entire pancreato-biliary region and mimics pancreatic cancer. Currently, there are no definitive criteria for pre-operative diagnosis, so it is very difficult for one to avoid resection.

Hereditary pancreatic endocrine tumours.

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.

Molecular diagnosis of early pancreatic ductal adenocarcinoma in high-risk patients.

The prevalence of pancreatic cancer in the general population is too low--even in high-prevalence areas such as Northern Europe and North America (8-12 per 10(5) population)--relative to the diagnostic accuracy of present detection methods to permit primary screening in the asymptomatic adult population. The recognition that the lifetime risk of developing pancreatic cancer for patients with hereditary pancreatitis (HP) is extremely high (20% by the age of 60 years and 40% by the age of 70 years) poses considerable challenges and opportunities for secondary screening in those patients without any clinical features of pancreatic cancer. Even for secondary screening, the detection of cancer at a biological stage that would be amenable to cure by surgery (total pancreatectomy) still requires diagnostic modalities with a very high sensitivity and specificity. Conventional radiological imaging methods such as endoluminal ultrasound and endoscopic retrograde pancreatography, which have proved to be valuable in the early detection of early neoplastic lesions in patients with familial pancreatic cancer, may well be applicable to patients with HP but only in those without gross morphological features of chronic pancreatitis (other than parenchymal atrophy). Unfortunately, most cases of HP also have associated gross features of chronic pancreatitis that are likely to seriously undermine the diagnostic value of these conventional imaging modalities. Pre-malignant molecular changes can be detected in the pancreatic juice of patients. Thus, the application of molecular screening in patients with HP is potentially the most powerful method of detection of early pancreatic cancer. Although mutant (mt) K-ras can be detected in the pancreatic juice of most patients with pancreatic cancer, it is also present in patients with non-inherited chronic pancreatitis who do not progress to pancreatic cancer (at least in the short to medium term), as well as increasingly in the older population without pancreatic disease. Nevertheless, the presence of mt-K-ras may identify a genuinely higher-risk group, enabling additional diagnostic imaging and molecular resources to be focussed on such a group. What is clear is that prospective multi-centre studies, such as that being pursued by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC), are essential for the development of an effective secondary screening programme for these patients.

Cost effectiveness of detecting Barrett's cancer.

BACKGROUND: Screening Barrett's oesophagus is controversial owing to a large variation in the reported incidence of neoplastic change and lack of evidence that screening improves tumour prognosis. AIMS: To determine the incidence of Barrett's cancer, its cost of detection, and stage of disease at time of diagnosis. PATIENTS AND METHODS: Data from our surveillance programme have been reviewed to assess the incidence of malignant change, tumour stage at diagnosis, and the cost per cancer detected. RESULTS: 166 patients had annual endoscopic surveillance. Six patients (five men) developed cancer-an incidence of one cancer per 59 male and 167 female patient-years of follow up. The screened group had a significantly earlier stage than a control group of unscreened cancers (p < 0.05). The cost of detecting one cancer was Pounds 14 868 for men and Pounds 42 084 for women. CONCLUSIONS: The cost of screening for Barrett's cancer is high but may be justified on the basis of the high incidence of detecting early stage disease.

Familial coexistence of achalasia and non-achalasic oesophageal dysmotility: evidence for a common pathogenesis.

In five of seven siblings of healthy parents, dysphagia developed during adolescence or early adult life. A barium swallow was normal in one patient but showed appearances considered to be consistent with achalasia in all others. Oesophageal manometry was successfully performed in four of the five patients, including the patient with symptoms but normal radiological appearance. One patient had achalasia, two had oesophageal body motor dysfunction associated with a hypertensive, but normally relaxing lower oesophageal sphincter, and one had diffuse oesophageal spasm alone. The occurrence of three different oesophageal dysmotility disorders within members of a single sibship suggests that these conditions are intimately related and probably genetically determined as an autosomal recessive trait.

A study of the penetration of meropenem into bile using endoscopic retrograde cholangiography.

One gram of meropenem was administered as prophylaxis to patients undergoing endoscopic retrograde cholangiography (ERC) in a study of the bile pharmacokinetics of this agent. Twenty-four patients were evaluated and a single bile sample was collected from each one during ERC at different time intervals following intravenous infusion. Bile concentrations after the dose ranged from 0.7 to 25.7 mg/L (mean 11.1) and exceeded the MIC90s for the pathogens most commonly associated with biliary tract infections for up to 203 mins. The bile concentrations of 13 patients with biliary tree obstruction were compared with those of 11 patients without obstruction. Bile concentrations in excess of the MIC90s for the predominant pathogens were achieved in both groups; a positive correlation between meropenem bile concentration and the time of dose administration was demonstrable only for the obstructed group. ERC may be a useful technique for biliary pharmacokinetic studies.

Liver blood flow: non-invasive estimation using a gamma camera.

A non-invasive radioisotope technique for the measurement of total liver blood flow (TBF) is described. The method requires the use of two intravenously administered tracers, 99mTc (technetium 99m) human serum albumin (HSA) and 99mTc colloid. Computer analysis of first-pass time activity curves for HSA for liver and lung tissues yields values for the arterial and portal contributions to liver blood flow, from which TBF can be determined. These values are then corrected for attenuation using the images of the colloid distribution. The use of the method is illustrated in 17 subjects. Assumptions, limitations and possible applications of the technique are discussed.

Clinical features, pathophysiology and relevance of portal hypertensive gastropathy.

The frequency and importance of gastric mucosal lesions in patients with portal hypertension have been increasingly recognized in recent years. This article describes the clinical and endoscopic features of portal hypertensive gastropathy and reviews the current state of knowledge concerning the pathophysiology and treatment of the disorder.

Prophylactic sclerotherapy for esophageal varices: long-term results of a single-center trial.

Survival after prophylactic sclerotherapy was assessed in a single-center study involving 99 cirrhotic (41 alcoholic) patients enrolled over 8-yr. The wedged hepatic vein pressure gradient was measured; those with pressure greater than or equal to 12 mm Hg were randomized to receive sclerotherapy or no treatment. The rest were not randomized. Patients in all three groups who bled were treated with emergency endoscopy and sclerotherapy. Stratification according to presence of ascites was also undertaken. Median follow-up was 61 mo (range = 14 to 107 mo). Survival among unrandomized patients was significantly longer than among randomized patients (p less than 0.006), but there was no significant difference between those treated by sclerotherapy and the controls (p = 0.27). Alcoholic cirrhotic patients undergoing sclerotherapy had better 2-yr survival than did the controls (80% vs. 43%; p = 0.09), but this benefit was not sustained at 5 yr. Survival in the nonalcoholic patient groups was identical. Only 10 of 50 deaths were caused by variceal bleeding. Forty-eight percent of patients with large varices bled, compared with 20% of patients with small varices. Wedged hepatic vein pressure less than 12 mm Hg accurately identified alcoholic patients at low risk of variceal bleeding but not nonalcoholic patients. Only four episodes of variceal bleeding were attributable to elective sclerotherapy. We conclude that in our population, prophylactic sclerotherapy alone does not improve survival. The discrepancy in survival between alcoholic and nonalcoholic cirrhotic patients suggests that factors other than variceal hemorrhage may be responsible for the difference.

Comparison of a dimethicone/antacid (Asilone gel) with an alginate/antacid (Gaviscon liquid) in the management of reflux oesophagitis.

Fifty-three patients with symptomatic reflux oesophagitis were entered into a single centre randomized study comparing the effects of a dimethicone/antacid (Asilone Gel) and an alginate/antacid (Gaviscon liquid) on symptoms and endoscopic changes over an 8-week period. Both treatments significantly improved heartburn, acid regurgitation and flatulence. Dimethicone/antacid but not alginate/antacid, produced a significant improvement in oesophagitis, oesophageal ulceration and histological grade of inflammation over the 8-week treatment period so that 14 patients treated with dimethicone/antacid and 10 with alginate/antacid had normal endoscopic oesophageal appearances at the end of the study. The difference in improvement between the two patient groups did not reach significance however, except for dimethicone/antacid improving histological changes (P less than 0.05). These findings suggest that dimethicone/antacid and alginate/antacid are equally effective in treating symptomatic reflux oesophagitis although dimethicone/antacid may have an advantage in improving oesophageal histological appearances.

A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites.

We report a randomised trial in 40 consecutive patients with diuretic refractory ascites comparing our standard therapy of ascites recirculation (Rhodiascit apparatus) with the newly proposed method of daily paracentesis (3-4 litre) and intravenous albumin infusion. A mean of five (range 2-13) paracenteses removed 13.3 (2.0-36.0) l of ascites. 12 (5-32) h of recirculation produced 6.0 (2.0-12.0) l of waste. A significant diuresis occurred in 14 recirculation patients compared to four treated by paracentesis. No significant changes in electrolyte levels or renal function occurred. Complications were commoner with paracentesis (12) than with recirculation (5). Following recirculation, 18 patients were discharged after 7 (2-21) days; significantly (p less than 0.04) shorter than after paracentesis (11 (4-34) days, 16 discharges). Ascites reaccumulation and survival were identical in both groups. Fewer complications, shorter hospital stay and lower consumables costs (recirculation 240 pounds, paracentesis 400 pounds) make ascites recirculation an attractive therapeutic option to daily paracentesis and intravenous albumin in diuretic refractory ascites.

Anorectal varices, haemorrhoids, and portal hypertension.

In a prospective study of 100 consecutive patients with cirrhosis, 44% had anorectal varices. The prevalence of anorectal varices rose with progression of portal hypertension; it was 19% in cirrhotic patients without portal hypertension compared with 59% in those who had bled from oesophageal varices. There was no evidence that endoscopic sclerotherapy directly increased the prevalence of anorectal varices. Haemorrhoids occurred independently of anorectal varices and their presence was unrelated to the degree of portal hypertension. These data provide further evidence that haemorrhoids and anorectal varices are separate and distinct entities. However, both can bleed and careful examination is essential to prevent misdiagnosis and inappropriate treatment.