Endoscopic minor papilla sphincterotomy in patients with complete pancreas divisum and acute recurrent pancreatitis: a metanalysis.

BACKGROUND AND AIMS: Pancreas divisum (PD) is a congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic minor papilla sphincterotomy (MiES) is the most common procedure performed in the management of PD-related ARP. The aim of this study is to perform a meta-analysis estimating the efficacy and the safety of MiES in the management of patients with PD-related ARP. METHODS: A research was performed in Pubmed, EMBASE and Web of science, the studies were reviewed and selected according to inclusion and exclusion criteria. Evaluation of Heterogeneity and publication bias was performed, and a random effect model was used to estimate the effect size of each study. RESULTS: One hundred and thirteen articles were selected and reviewed, 13 met the inclusion criteria. All the studies were retrospective with a mean follow-up duration of 45.9 months. A total of 323 patients with PD-related ARP treated with MiES were included in the meta-analysis. The overall clinical success rate of MiES (defined as no further episodes of ARP, reduction of episodes of ARP, or improvement in quality of life) was of 77% (95%CI: 72%-81%; p = 0.30). Evaluating only the studies with clinical success rate defined as "no further AP in the follow-up" the clinical success rate was of 69.8% (95%CI: 61.3%-77.2%; p = 0.57), while evaluating the studies with other definitions (reduction of episodes of ARP or improvement in quality of life) the clinical success rate was of 81.2% (95%CI: 75.2%-86.1%; p = 0.45). The common fixed effects model disclosed a 25.5% overall adverse events rate (95%CI: 19.3%-32.8%; p = 0.42): acute pancreatitis in 14.3% (95%CI: 9.7%-20.6%; p = 0.36), bleeding in 5.6% (95%CI: 2.9%-10.4%; p = 0.98), and other adverse events in 5.6% (95%CI: 2.9%-10.4%; p = 0.67). CONCLUSION: MiES is an effective and relatively safe treatment in the management of PD-related ARP. The retrospective nature of the studies selected is the main limitations of this metanalysis. Prospective trials are needed to confirm these data.

Endoscopic pancreatic sphincterotomy in patients with IPMN-related recurrent pancreatitis: A single center experience.

BACKGROUND: Acute recurrent pancreatitis (ARP) is a rare manifestation of Intraductal Papillary Mucinous Neoplasms (IPMN) of the pancreas; ARP is a relative indication for pancreatic surgery in the setting of IPMN. Endoscopic pancreatic sphincterotomy (EPS) has been described as a minimal invasive treatment to reduce the episodes of ARP secondary to mucus migration in IPMN. METHODS: patients with IPMN-related ARP treated with ESP from January 2004 to December 2020 were retrospectively selected. Clinical and technical data were recorded. A clinical follow-up (minimum 12 months) was performed to assess the number of episodes of AP occurring after EPS. RESULTS: 25 patients were included. The mean follow-up after ESP was 93.4 months (SD± 56.6). The mean number of AP before and after EPS were respectively 3.29 (SD ± 1.04) and 0.51 (SD ± 0.71). A complete response (no further episodes of AP) and a partial response (>50% reduction of AP episodes) were obtained in 64% and 24% of the cases, respectively, with an overall response rate of 88%. One post-EPS bleeding and one minor-papilla stenosis were reported and were endoscopically managed. Two patients underwent pancreatic resection for the occurrence of high-risk stigmata for cancer progression. CONCLUSIONS: EPS is a safe and effective treatment to reduce the number of episodes of AP in selected patients with IPMNs-related ARP. Prospective trials are needed to confirm these data.

The impact of the multidisciplinary tumor board (MDTB) on the management of pancreatic diseases in a tertiary referral center.

BACKGROUND: The implementation of multidisciplinary tumor board (MDTB) meetings significantly ameliorated the management of oncological diseases. However, few evidences are currently present on their impact on pancreatic cancer (PC) management. The aim of this study was to evaluate the impact of the MDTB on PC diagnosis, resectability and tumor response to oncological treatment compared with indications before discussion. PATIENTS AND METHODS: All patients with a suspected or proven diagnosis of PC presented at the MDTB from 2017 to 2019 were included in the study. Changes of diagnosis, resectability and tumor response to oncological/radiation treatment between pre- and post-MDTB discussion were analyzed. RESULTS: A total of 438 cases were included in the study: 249 (56.8%) were presented as new diagnoses, 148 (33.8%) for resectability assessment and 41 (9.4%) for tumor response evaluation to oncological treatment. MDTB discussion led to a change in diagnosis in 54/249 cases (21.7%), with a consequent treatment strategy variation in 36 cases (14.5%). Change in resectability was documented in 44/148 cases (29.7%), with the highest discrepancy for borderline lesions. The treatment strategy was thus modified in 27 patients (18.2%). The MDTB brought a modification in the tumor response assessment in 6/41 cases (14.6%), with a consequent protocol modification in four (9.8%) cases. CONCLUSIONS: MDTB discussion significantly impacts on PC management, especially in high-volume centers, with consistent variations in terms of diagnosis, resectability and tumor response assessment compared with indications before discussion.

Endoscopic hemostasis with fibrin glue for refractory postsphincterotomy and postpapillectomy bleeding.

BACKGROUND: Bleeding is a feared complication of endoscopic sphincterotomy and papillectomy. Fibrin glue has been proposed as an effective adjunct in securing hemostasis. However, its use has been limited by the risk of early occlusion of the injecting needle, and its role has not been defined in the setting of refractory post-ERCP bleeding. We present a modified technique of endoscopic hemostasis with diluted fibrin glue in the setting of postsphincterotomy and postpapillectomy bleeds. OBJECTIVE: We aimed to verify that diluted fibrin glue can be easily and successfully injected and is effective in the endoscopic treatment of refractory post-ERCP bleeding. DESIGN: Case series. SETTING: A tertiary-care academic medical center. PATIENTS: Six patients with refractory post-ERCP bleeding were treated (3 after sphincterotomy and 3 after papillectomy) with fibrin glue injection. INTERVENTION: Endoscopic hemostasis with diluted fibrin glue injection. MAIN OUTCOME MEASUREMENTS: Successful endoscopic hemostasis with diluted fibrin glue injection. RESULTS: One session of fibrin glue injection stopped the refractory post-ERCP bleeding in all 6 patients. LIMITATION: Small number of patients. CONCLUSION: This case series provides evidence that our modified injection technique of diluted fibrin glue allowed an easy submucosal injection and may be considered to be an effective endoscopic modality to treat refractory post-ERCP bleeding.

Endoscopic gallbladder drainage for acute cholecystitis: technical and clinical results.

BACKGROUND AND STUDY AIMS: Cholecystectomy is the standard treatment for acute cholecystitis while percutaneous drainage is reserved for high-risk patients. The aim of the present study was to assess the technical success rate and clinical efficacy of endoscopic gallbladder drainage in patients with acute cholecystitis. PATIENTS AND METHODS: A total of 35 consecutive patients with acute cholecystitis and without residual common bile duct obstruction were retrospectively identified. Patients were stratified according to the pathogenesis and stages of acute cholecystitis, and the morphology of the cystic duct and/or its insertion in the common bile duct. Primary outcomes were technical success and early and late clinical success. RESULTS: Endoscopic retrograde cholangiopancreatography (ERCP) was performed within the first 72 hours in 19 patients (54%). Technical success was achieved in 29 patients (83%); drainage was nasocholecystic in 21 of these (72%), plastic stenting in 6 (21%), and a combined method in 2 (7%). The pathogenesis and stage of acute cholecystitis, and the morphology both of the cystic duct and its insertion in the common bile duct, did not influence technical success. Clinical success was achieved in 24 cases (83%) after a median of 3 days (range 2-12). Four patients (14%) died within 3 days due to septic complications, and one accidentally removed the nasocholecystic drain after 24 hours. Late results, available in 21 patients after a median follow-up of 17 months, showed relapse of acute cholecystitis in 2 (10%) (both with stents) and of biliary pain in 2 patients (10%), both of whom had nasocholecystic drainage. CONCLUSIONS: Endoscopic gallbladder drainage seems feasible and effective in resolving acute cholecystitis, but only as a temporary measure because of a 20% relapse rate in long-term follow-up. Prospective studies are necessary to identify which patients would benefit most from this endoscopic technique in the short and long term.

Endoscopic treatment of chronic pancreatitis in pediatric population: Long-term efficacy and safety.

Background: Chronic pancreatitis (CP) in children is an inreasingly recognized disease. Objective: The purpose of study was to analyse the safety and long-term efficacy of endoscopic treatment in children with CP. Methods: Records of 38 patients aged <18 years, referred to the Digestive Endoscopy Unit at Catholic University, Fondazione Policlinico "A. Gemelli" IRCCS between 1991 and 2017, were reviewed. Abdominal pain, analgesia and number of episodes of acute pancreatitis in the pre- and post- endoscopic retrograde cholangiopancreatography (ERCP) period were evaluated. Need for surgery was assessed. Therapeutic intervention data and complications were interrogated. Results: In total 158 ERCPs were performed. Median post-ERCP follow-up was 7 years. The majority of patients had CP type IV (47%) and type Ib (37%) (Cremer's classification). Major papilla pancreatic sphincterotomy was performed in 47%, major and minor in 24% and minor in 29% of patients. Stones/plugs were removed in at least one ERCPs in 66% individuals. Eleven out of 38 patients had stricture of the pancreatic duct; these were dilated and stented in 5/11 and stented in 6/11. Five complications were recorded (3%). Severity and frequency of abdominal pain improved significantly; p < 0.001. Use of analgesia and number of episodes of acute pancreatitis decreased significantly; p < 0.001. One child required subsequent surgery. Conclusion: Endoscopic management of symptomatic CP in children is safe and effective.

No difference between supine and prone position for ERCP in conscious sedated patients: a prospective randomized study.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is usually performed with the patient prone or in the left lateral position. The supine position could be more comfortable and may facilitate airway management. On the other hand, technical difficulties and a greater risk of adverse cardiorespiratory events have been shown when ERCP is performed in a supine patient. Our aim was to assess, in a tertiary referral center, the differences between performing ERCP with the patient supine or prone, in terms of technical features and complications both during and after the procedure. PATIENTS AND METHODS: Between December 2005 and May 2006, 120 patients (66 female, mean age 62 years) who had an intact papilla and were candidates for therapeutic ERCP were prospectively randomized to undergo ERCP under conscious sedation with midazolam, in the prone (n = 60) or supine (n = 60) position, by an expert endoscopist (tutor) or a trainee. The following parameters were recorded: difficulty of cannulation and difficulty of ECRP procedure, time needed to visualize the papilla, time needed to achieve opacification and cannulation, exam duration, episodes of tachy/bradycardia and desaturation, episodes of duodenoscope displacement into the stomach, and complications. RESULTS: Ninety-eight patients underwent ERCP for benign disease and 22 for malignant biliary strictures. The ERCP success rate was 98.3 % in the tutor group and 43.3 % in the trainee group. No significant differences were found between the two groups of operators (tutors and trainees) in the recorded parameters and complication rates encountered in prone versus supine patients. CONCLUSION: Our results show that ERCP success rates and complications (intraoperative and postoperative) are similar whether ERCP is performed with the patient prone or supine, even when operators are of differing skill levels. Training, technique, and a proper learning phase are recommended in order to perform ERCP with no differences whether the patient is prone or supine.

Active thymopoiesis in idiopathic chronic pancreatitis.

BACKGROUND/AIMS: Cellular immunity has a pivotal role in the pathogenesis of chronic pancreatitis (CP), resulting in pancreas infiltration by T-cells. Studies on systemic immunity are few and contradictory. One study reported a decrease of naive CD45RA+ cells. The presence of naive T cells, detected as recent thymic emigrants (RTEs), is evaluated with a new molecular technique by using real-time PCR to detect the T-cell receptor excision circles (TREC). To elucidate the role of naive T-cells in the pathogenesis of CP, we investigated the percentage of sj-TREC in CP patients. PATIENTS: Thirty CP patients were studied and compared to 30 sex- and age-matched healthy volunteers. METHODS: Genomic DNA was isolated from peripheral blood mononuclear cells (PBMC) of each patient. RTEs were evaluated by measuring sj-TREC by real-time PCR. RESULTS: The mean percentage of sj-TREC+ cells present in CP was not significantly different from that of control group (0.02319% vs 0.02338%, respectively). CONCLUSION: Our data show that naive TREC+ cells are normally represented in CP. The presence of active thymopoiesis may be the underlying mechanism resulting in continuous production of T-cells, responsible of maintaining the inflammatory process.

Combined endoscopic stent insertion in malignant biliary and duodenal obstruction.

BACKGROUND AND STUDY AIMS: Self-expandable metal stents (SEMS) are an effective palliative treatment for malignant biliary and duodenal strictures. Combined biliary and duodenal stenting remains a technical challenge, however. The aim of this study was to evaluate the technical feasibility of an endoscopic approach to double stenting of malignant biliary and duodenal strictures. PATIENTS AND METHODS: Consecutive patients referred for palliative gastroduodenal and biliary stenting were followed up prospectively. Patients' demographic characteristics, the site and nature of the strictures, success rates, complications, and survival time were recorded. RESULTS: A total of 64 patients underwent double stenting. In 46 patients, biliary obstruction occurred before the onset of duodenal obstruction (by a median of 107 days) (group 1); in 14 patients, biliary obstruction occurred concurrently with duodenal obstruction (group 2); and in four patients the duodenal obstruction preceded the biliary obstruction (by a median of 121 days) (group 3). The duodenal strictures were proximal to the papilla in 31 patients, adjacent to the papilla in 25 patients and distal to the papilla in eight patients. The majority of biliary strictures were in the middle or distal third of the bile duct (in 52/64 patients). Duodenal SEMS were successfully deployed in all patients. Combined endoscopic stenting was successful in 100% of patients in group 1, 86% of patients in group 2, and in 100% of patients in group 3. Taking the three groups together, early complications occurred in 6% of patients and late complications occurred in 16% of patients. The overall median survival after combined stenting was 81 days (range 2-447 days). CONCLUSIONS: Combined endoscopic biliary and duodenal SEMS insertion is safe and effective for palliation in malignant biliary and duodenal obstruction. Biliary stenting through the mesh of the duodenal SEMS is technically feasible and has a high success rate.

Quantal mechanism of transmitter release during progressive depletion of the presynaptic stores at a ganglionic synapse. The action of hemicholinium-3 and thiamine deprivation.

In the present experiments we interfered with the mechanism of acetylcholine (ACh) synthesis in the rat superior cervical ganglion by impairing the supply of either the choline group (hemicholinium no. 3 [HC-3]treatment) or the acetyl group (thiamine deprivation). Under both conditions stimulation causes in the ganglion a progressive decline in ACh output associated with a depletion of transmitter tissue content. ACh release from the terminals of a single preganglionic fiber was estimated from the quantum content value of the evoked excitatory postsynaptic potentials (EPSP's) recorded intracellularly in the ganglion neuron under test. The present observations indicate that Poisson statistics describe transmitter release at either low or high release levels. Furthermore, the progressive decline in the rate of ACh output occurring during repetitive stimulation is shown to correspond to a progressive decrease in the number of transmitter quanta released per impulse and not to any modification in the size of individual quanta. Some 8,000 transmitter quanta proved to represent the presynaptic transmitter store initially present in those terminals on a neuron that are activated by stimulation of a single preganglionic fiber. Speculations are considered about synaptic efficacy and nerve connections in rat autonomic ganglia. It is suggested that six preganglionic fibers represent the mean input to a ganglion neuron.

Combined modality treatment in unresectable extrahepatic biliary carcinoma.

PURPOSE: Cancers of the extrahepatic biliary tract are rare. Surgical resection is considered the standard treatment, but is rarely feasible. Several reports of combined modality therapy, including external beam radiation, often combined with chemotherapy and intraluminal brachytherapy, have been published. The purpose of this study was to evaluate the effect of chemoradiation plus intraluminal brachytherapy on response, local control, survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: From February 1991 to December 1997, 20 patients (14 male, 6 female; mean age 61 +/- 12 years; median follow-up 71 months) with unresectable (16 patients) or residual (4 patients), nonmetastatic extrahepatic bile tumors (common bile duct, 8; gallbladder, 1; Klatskin, 11) received external beam radiation (39.6-50.4 Gy); in 19 patients, 5-fluorouracil (96-h continuous infusion, days 1-4 at 1,000 mg/m(2)/day) was also administered. Twelve patients received a boost by intraluminal brachytherapy using (192)Ir wires of 30-50 Gy, prescribed 1 cm from the source axis. RESULTS: During external beam radiotherapy, 8 patients (40%) developed grade 1-2 gastrointestinal toxicity. Four patients treated with external-beam plus intraluminal brachytherapy had a clinical response (2 partial, 2 complete) after treatment. For the total patient group, the median survival and time to local progression was 21.2 and 33.1 months, respectively. Distant metastasis occurred in 10 (50%) patients. Two patients who received external beam radiation plus intraluminal brachytherapy developed late duodenal ulceration. Two patients with unresectable disease survived more than 5 years. CONCLUSION: Our data suggest that chemoradiation plus intraluminal brachytherapy was relatively well-tolerated, and resulted in reasonable local control and median survival. Further follow-up and additional research is needed to determine the ultimate efficacy of this regimen. New chemoradiation combinations and/or new treatment strategies (neoadjuvant chemoradiation) may contribute, in the future, to improve these results.

Intraluminal brachytherapy in the treatment of pancreas and bile duct carcinoma.

PURPOSE: A new method of palliation of malignant obstructive jaundice is presented. METHODS AND MATERIALS: Twelve patients with carcinoma of the extrahepatic bile ducts (EHBD-five patients) or pancreatic head (PH-seven patients) received radiation therapy between 1988 and 1991. Percutaneous transhepatic biliary drainage was performed in four EHBD patients and an endoprosthesis was placed during endoscopic retrograde cholangiopancreatography (ERCP) in the other eight patients. All 12 received intraluminal brachytherapy (ILBT): 20-50 Gy calculated at 1 cm from the Iridium-192 (192Ir) wire. In four PH patients the source was placed in the duct of Wirsung; in the other eight patients ILBT was performed via the common bile duct. Five of the seven PH patients and one of the five EHBD patients received External Beam Radiation Therapy (EBRT): 26-50 Gy, alone or with concomitant 5-Fluorouracil (5-FU). RESULTS: Cholangitis occurred in six patients. Three PH patients treated with EBRT+ILBT developed gastrointestinal toxicities. With a minimum follow-up of 18 months, median survival times were 14 months (EHBD) and 11.5 months (PH); one of the seven PH patients is alive (29 months) and two of the EHBD patients are alive (18 and 43 months). All patients had satisfactory control of jaundice. CONCLUSIONS: The results in the EHBD patients suggest that the addition of ILBT after biliary drainage prolongs survival. Further experience is necessary to determine whether ILBT in the common bile duct and/or in the duct of Wirsung may be, in PH patients, an alternative boost technique to Interstitial Brachy-therapy (IBT) or Intraoperative Electron Beam Radiation Therapy (IOEBRT).

Some properties of the transmitter release mechanism at the rat ganglionic synapse during potassium stimulation.

In the present investigation a study has been made using intracellular recordings in the rat superior cervical ganglion of the mode of transmitter release induced by raised external potassium ion concentration (40 mM), after acetylcholine synthesis has been blocked by hemicholinium-3. It is shown that the progressive decline in the rate of acetylcholine output from the ganglion is related to a decrease in the number of quanta being released. Furthermore, under these conditions there is no evidence for a reduction in the size of the transmitter quantum. The statistical foundations of the quantal release process at the rat ganglionic synapse have been investigated by comparing the distribution of the number of miniature EPSPs during successive constant time intervals in the tracings with the corresponding Poisson and binomial predictions. Analyses have shown that the probability for a quantum to be released is so small as to produce a binomial distribution of responses indistinquishable fro- the corresponding Poisson distribution, both at the beginning of the potassium-induced quantum discharge and when transmitter release level is low after exhaustion of acetylcholine tissue content.

Post-tetanic spontaneous spike activity in rat sympathetic neurons exposed to low potassium ion concentration.

Preganglionic tetanic stimulation (30 sec at 50/sec) of rat superior cervical ganglia, performed in the presence of reduced external potassium concentration (0-1 mM), is followed by a long-lasting postganglionic afterdischarge which fails to appear if stimulation is repeated in normal (5.6 mM) postassium solution. Intracellular recordings revealed that tetanus is followed by 15-30 mV membrane hyperpolarization when the neuron is exposed to normal concentrations of potassium. Conversely, after the ganglion is soaked in low potassium, stimulation results in long-lasting depolarization of the nerve cell with the consequent appearance of spontaneous spikes. This effect is reversed on returing to normal external potassium. Spontaneous activity also occurs after antidromic activation of the cell. It is suggested that tetanus causes sodium loading of the neuron, which leads to stimulation of an electrogenic sodium pump. If potassium is available, the membrane will hyperpolarize, whereas depolarization and pacemaker activity ensues if external potassium is removed. The electrogenic sodium pump thus endows. the rat sympathetic neuron with a mechanism which enables it excitability to be controlled.

Evidence for increased release of prostaglandins of E-type in response to orthodromic stimulation in the guinea-pig superior cervical ganglion.

Prostaglandins of the E type (PGEs) stimulate cyclic adenosine 3',5'-monophosphate (cAMP) biosynthesis both in isolated preparations of rat, guinea-pig and rabbit superior cervical ganglia (SCG) and in calf SCG slices. Electrical stimulation of preganglionic nerve fibers of the guinea-pig SCG remarkably increased PGE release and cAMP biosynthesis. These effects were blocked by reducing the Ca2+ to Mg2+ ratio in the incubation medium. Atropine (1 microM) and phentolamine (10 microM) inhibited PGE biosynthesis and significantly reduced cAMP levels.

Storage and release of acetylcholine in the isolated superior cervical ganglion of the rat.

The storage and release of acetylcholine and choline were studied in the isolated superior cervical ganglion of the rat by a radioenzymic method. The acetylcholine and choline contents were 202.2 +/- 5.1 and 624.7 +/- 20.2 pmole/ganglion, respectively. The transmitter tissue store was unaffected during 1 h of superfusion in choline--Krebs solution, while a 20% decrease was exhibited after 2 h and then remained approximately stable. Conversely, choline content declined to 50% within 1 h and further to 37% of the original level by 4 h. About 24% of the choline assayed in the intact preparation is located in the connective sheath. Preganglionic nerve stimulation at 10--20/sec or potassium stimulation (40 mM KCl) invariably decreased the transmitter tissue stores by 25--45%; such a depletion is independent of the presence or absence of external choline. By contrast, the presence of choline proved to be a prerequisite for the efficient release of acetylcholine from eserinized ganglia during continuous 10/sex stimulation. A drastic depression in the acetylcholine release is described which is related to the time of preincubation of the ganglia with eserine prior to stimulation. Indeed, a 30 min exposure to eserine, compared with a 5 min period, resulted in a 4-fold decrease in the steady output rate. Under optimal conditions, the initial volley output at 10/sec was 1.3 X 10(-4) of the releasable transmitter pool and 1.9 X 10(-4) during the steady-state output. These results are discussed in the light of the electrophysiological knowledge of the quantal release process at the ganglionic synapse.

Quantitative evaluation of alpha- and beta-adrenoceptor modulation of [3H]choline release in guinea pig superior cervical ganglia.

[3H] Overflow evoked by 5 min supramaximal preganglionic stimulation at 1 pps has been studied in isolated guinea pig superior cervical ganglion preparations preincubated with [3H]choline. At 15 microM norepinephrine (NE) reduced both the [3H]choline overflow and endogenous acetylcholine release by 59.4 and 54.1% respectively; the dose-response curve for NE inhibitory action is described. Evidence is given that endogenous catecholamines effectively reduce ACh release from the ganglia. After blocking the inhibitory action of endogenous NE, a significant beta-adrenoceptor-mediated facilitatory effect on ACh release could be observed. Preincubation of the ganglia with different combinations of alpha 1 and alpha 2 agonists (phenylephrine, 10 microM and clonidine, 1 microM respectively) and antagonists (prazosin, 10 microM and yohimbine, 3 microM) showed that the adrenoceptors involved in alpha-mediated NE inhibition of ACh output are exclusively of the alpha 2-type.

Therapeutic equivalence of inhaled beclomethasone dipropionate with CFC and non-CFC (HFA 134a) propellants both delivered via the Easibreathe inhaler for the treatment of paediatric asthma.

Chlorofluorocarbon (CFC)-containing inhalers for use in the treatment of asthma are to be phased out under the terms of the Montreal Protocol (1). In this multi-centre, randomized, double-blind study, the therapeutic equivalence of two formulations of beclomethasone dipropionate (BDP) containing CFC or non-CFC (HFA134a) propellant, both delivered via the Easibreathe (Norton Healthcare Ltd, London, U.K.) inhaler, was determined in 229 asthmatic children. Each child received 100 microg doses of BDP (containing either CFC or HFA propellant) twice daily for 12 weeks. Both CFC and HFA formulations produced statistically and clinically significant improvements in patient's lung function and symptom scores when administered via the Easibreathe inhaler. The improvements in mean morning peak expiratory flow (PEF) were 41 l min(-1) and 34 l min(-1) for the BDP-HFA and BDP-CFC products respectively (P<0.001) and for mean evening PEF the improvements were 38 l min(-1) and 38 l min(-1), respectively (P<0.001). Similar findings were demonstrated for the other efficacy parameters. The two formulations were statistically equivalent with respect to efficacy. For mean morning PEF the estimated treatment difference (BDP-CFC/BDP-HFA ratio) was 102.6% (95% CI 99.1, 106.2). Similar equivalence was shown for the other efficacy parameters. Both products were well tolerated, with no difference in the adverse event profiles, effects on 24 h urinary cortisol or Candida colonisation. This study demonstrates that the new formulation of BDP with HFA-134a propellant is equivalent to and directly substitutable for BDP with the older CFC propellant in a dose for dose manner. This should enable a seamless transition from one product to the other when CFC containing products are eventually phased out. In addition this study has also shown that the Easibreathe inhaler is an effective delivery system for use with inhaled products for the treatment of asthma in children.

Endoscopic treatment of extrahepatic bile duct strictures in patients with portal biliopathy carries a high risk of haemobilia: report of 3 cases.

Extrahepatic portal venous obstruction can be associated with bile duct abnormalities, the entity being called portal biliopathy. Three cases are reported of extrahepatic bile duct strictures in patients with portal biliopathy who developed haemobilia during endotherapy. Although endoscopic therapy with stent placement can be successful in patients with portal biliopathy and could also lead to permanent stricture resolution, procedure-related haemobilia is not as uncommon as previously held. Shunt surgery could be a better option in fit patients, since it could provide definitive treatment in a young patient with an otherwise normal life expectancy.

Liver, pancreas and biliary tract enhanced lipoperoxidation products in pure pancreatic juice: evidence for organ-specific oxidative stress in chronic pancreatitis.

BACKGROUND: Oxygen-free radicalscan play a role in the development of chronic pancreatitis, altering the redox state with damage of cell constituents and decrease in antioxidant defences. AIMS: To measure levels of lipoperoxidation products, conjugated dienes and lipid hydroperoxides, in pure pancreatic juice and serum of chronic pancreatitis patients and compare them to that in controls. To investigate a possible correlation with serum indexes of pancreatic inflammation (amylase and lipase). PATIENTS: Pancreatic juice was collected during ERCP, after secretin stimulation, in 20 patients with chronic pancreatitis and 11 controls with biliary diseases. METHODS: Lipid hydroperoxide levels were determined with FOX2 method and measured as absorbance at 560 nm. Conjugated diene levels were measured using second-derivative spectroscopy. RESULTS: No substantial difference was present in serum levels of lipid hydroperoxides, conjugated dienes (in both isomeric forms) and isomer-ratio values between those of patients with chronic pancreatitis and controls. In pancreatic juice, there was a significant increase in lipid hydroperoxides and conjugated dienes levels (especially trans-trans isomers) in chronic pancreatitis patients compared with controls, with a decrease in cis-trans isomers and a significant difference in isomer-ratio values. CONCLUSIONS: Increased levels of lipid hydroperoxides and conjugated dienes in the pancreatic juice of chronic pancreatitis patients is indicative of an enhanced lipoperoxidation and antioxidants consumption in pancreatic tissue, confirmed by the decreased isomer-ratio values as an indirect index of decreased antioxidant capacity. The lack of significant difference in conjugated diene and lipid hydroperoxide levels in the serum of chronic pancreatitis patients versus that of controls suggests an oxidative stress limited to pancreatic tissue and indicative of an organ-specific pathology, confirmed by the parallel behaviour of oxidative parameters (lipid hydroperoxides and conjugated dienes) and indexes of pancreatic inflammation (amylase and lipase).