Pre-Endoscopy real-time PCR testing for SARS-CoV2 does not reduce health care workers infection and is associated with a higher reduction of endoscopic activity in an outpatient setting.

Objective: The role of pre-procedure SARS-CoV2 testing in digestive endoscopy is still debated. AGA guidelines recommend against pre-procedure testing considering low prevalence of SARS- CoV2 infection in the general population and low incidence of infection among endoscopy units Health Care Workers (HCWs). However, no studies have compared pre-procedure testing associated to symptom screening vs. symptom screening alone in reducing the risk of infection for HCWs. Main aim of the present study is to compare the risk of infection for HCWs in different Endoscopy Units adopting different pre-endoscopy screening and operating in two nearby hospital of the same region in Northern Italy in pre-vaccination period. For outpatients in the Endoscopy Unit of Trento (Unit 1) only pre-procedure symptom screening was performed, while in the Endoscopy Unit of Bolzano (Unit 2) pre-procedure symptom screening and negative pre-procedure real-time PCR were requested. Secondary aims were to assess the impact of pre-procedure real-time PCR testing on endoscopic activity and diagnostic delay. Design: Retrospective data collection on a prospectively maintained database was performed, including outpatient endoscopy procedures performed between June 1st 2020 and February 28th 2021 in Unit 1 and Unit 2. Results: No differences in terms of infection rate in HCWs have been identified in Unit 1 and Unit 2 (9.0 vs. 19.3% P=0.2) over a nine-month period. Moreover, in the unit performing pre- procedure real-time PCR before endoscopy a significantly higher reduction in endoscopic activity has been recorded (61.9% vs. 53.4%; P<0.01). In patients with positive real-time PCR, endoscopy was performed with a mean delay of 61.7 days (range 9-294) and 22.5% of them were lost at follow-up and did not undergo any endoscopic procedure in the following 12 months. Conclusions: This study supports the AGA recommendation suggesting that pre-endoscopy real-time PCR is an expensive and time-consuming procedure without proven benefits in an outpatient setting.

Extracorporeal shock wave lithotripsy for clearance of refractory bile duct stones.

BACKGROUND AND STUDY AIMS: Following endoscopic sphincterotomy, 90% of bile duct stones can be removed with a Dormia basket or balloon catheter. The removal can fail in patients with large stones, intrahepatic stones, bile duct strictures or a difficult anatomy. The aim of this retrospective study is to investigate the efficacy and safety of extracorporeal shock wave lithotripsy in fragmenting and allowing the extraction of bile duct stones that could not be cleared by routine endoscopic means including mechanical lithotripsy. PATIENTS AND METHODS: From 1989 to January 2005, we treated with extracorporeal shock wave lithotripsy 376 patients (133 males and 243 females, median age 71.4 years) with bile duct stones that were not removable following endoscopic sphincterotomy, using the extracorporeal shock wave lithotripsy Lithostar Plus machine built by Siemens Co. of Erlangen, Germany. Stone targeting was performed fluoroscopically following injection of contrast via nasobiliary drain or T-tube in 362 patients and by ultrasonography in eight patients. Residual fragments were cleared at endoscopic retrograde cholangiopancreatograhy. Two hundred and ten of the 370 patients treated (56.7%) showed only 1 stone, 57 (15.4%) showed 2, 45 (12.1%) showed 3, 58 (15.6%) showed more than 3 stones. The median diameter of the stones was 21mm (range 7-80mm). RESULTS: Complete stone clearance was achieved in 334 of the 376 patients who underwent the extracorporeal shock wave lithotripsy procedure (90.2%). Six patients (1.5%) dropped out of treatment during their first sessions, mainly because of intolerance. Each patient averaged 3.7 treatments (1-12), at an average rate of 3470 shocks per session (1500-5400), at an average energy level of 3.4mJ (1-7). Complications were recorded in 34 patients (9.1%); 22 patients experienced symptomatic cardiac arrhythmia, 4 haemobilia, 2 cholangitis, 3 haematuria, 3 dyspnoea; no deaths were associated with the procedure. CONCLUSIONS: Extracorporeal shock wave lithotripsy is a safe and effective therapy in those patients in whom endoscopic techniques have failed with a clearing rate of 90.2% of refractory bile duct stones with a low rate of complications.

Anastomotic configuration and mucosal 5-aminosalicyclic acid (5-ASA) concentrations in patients with Crohn's disease: a GISC study. Gruppo Italiano per lo Studio del Colon e del Retto.

OBJECTIVE: Recurrence of Crohn's disease quite inevitably occurs after resection of distal small bowel and proximal colon, involving the neoterminal ileum close to the anastomosis. Oral 5-aminosalicylic acid (5-ASA) administered soon after surgery delays recurrence and reduces its severity. We recently observed that in operated patients submitted to prophylactic treatment with oral 5-ASA the rate of recurrence was significantly higher in those with end-to-end anastomosis than in those with other types of anastomosis (end-to-side, side-to-side). The hypothesis investigated in the present study was that patients with end-to-side or side-to-side anastomosis would benefit from a higher mucosal concentration of 5-ASA with respect to patients with end-to-end anastomosis. Therefore, the mucosal 5-ASA concentration was measured in the perianastomotic area of both groups. METHODS: The study was carried out in 19 patients submitted to radical surgery for Crohn's ileitis or ileocolitis, under oral prophylactic treatment with 5-ASA (Asacol). All patients were on regular endoscopic follow-up and were free of recurrence. Two biopsies were collected 3 cm from the anastomosis, in the neoterminal ileum, and two biopsies were collected at the colonic site 3 cm below the anastomosis. 5-ASA concentrations (ng/mg) were measured in tissue homogenates by high-performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: The mucosal concentration of 5-ASA in the neoterminal ileum was significantly lower in patients with end-to-end anastomosis than in those with other types of anastomosis (median values: 29.4 ng/mg vs 92.9 ng/mg respectively; p < 0.001). Six of 10 patients (60%) with end-to-end anastomosis, but none of the nine patients with other types of anastomosis, showed 5-ASA mucosal concentrations <40 ng/mg at the neoterminal ileum. On the contrary, no patients with end-to-end anastomosis showed mucosal concentrations of 5-ASA >90 ng/mg, compared with the 57% of patients in the group with other types of anastomosis. No differences were observed for colonic biopsies. CONCLUSIONS: The different mucosal concentrations in these two groups may be explained by the difference in segmental transit time induced by the different anastomotic configurations. A slower preanastomotic transit time, demonstrated in patients with end-to-side or side-to-side anastomosis, could offer a prolonged contact time between the intestinal content and the mucosa, resulting in an increase in drug absorption.

Prevention of post-operative recurrence of Crohn's disease requires adequate mucosal concentration of mesalazine. Gruppo Italiano per lo Studio del Colon e del Retto.

BACKGROUND: Surgical resection of Crohn's disease is followed by early recurrence in a high percentage of patients. Mesalazine has been shown to be effective in the prevention of post-operative recurrence, but some 50% of patients under treatment recur at 3 years of follow-up. AIM: To establish whether the mucosal concentration of mesalazine might affect the development of post-operative recurrence. METHODS: Colon-ileoscopy was performed in 25 consecutive patients resected for Crohn's disease. The mean time from surgery was 14 months. After the operation, all patients were taking oral mesalazine (Asacol, 2.4 g/day). Ten patients showed signs of endoscopic recurrence (apthae, ulcers, narrowing of the lumen) in the neoterminal ileum, five of whom also showed juxta-anastomotic colonic involvement. Fifteen patients were free of recurrence. At endoscopy, four biopsies were taken from the perianastomotic area (two specimens at the ileal site and two specimens at the colonic site of the anastomosis). The specimens were weighed and immediately frozen at -80 degrees C. Mesalazine concentration (ng/mg) was measured in tissue homogenates by high- performance liquid chromatography with electrochemical detection. Fisher's exact test was used for the statistical analysis. RESULTS: The mean value of mucosal mesalazine concentration, expressed as ng/mg of tissue, was significantly lower in patients with recurrence than in those without recurrence both in the ileum (mean +/- s.d.: 21.6+/-28.3 vs. 70.9+/-47.4; P = 0.007) and in the colon (25.8+/-26.4 vs. 60.3+/-32.5; P = 0.010). CONCLUSIONS: The mucosal concentration of mesalazine in the juxta-anastomatic area is significantly lower in patients with recurrence than in those free of recurrence. These data could suggest an association between mucosal mesalazine concentrations and the clinical effectiveness of the drug.

[Diet and drugs in the therapy of nonorganic dyspepsia: the hypothesis and factual data]. / Dieta e farmaci nella terapia della dispepsia non organica: ipotesi e dati di fatto.

Non-organic dyspepsia, although not frequently reported, is still a disorder which is difficult to classify in nosographic and physiopathological terms, a fact which inevitably influences the indications for its treatment. Non-pharmacological treatment of non-organic dyspepsia includes changes in dietary and behavioural habits which, even if established on empirical grounds, play a far from ancillary role. When considered appropriate, pharmacological treatment must be formulated solely on the basis of controlled clinical trials vs placebo given the well-known significance of the placebo effect in this and other so-called "functional" diseases. The therapeutic strategies which are most subject to verification are based on the one hand on the neutralisation or inhibition of gastric acid secretion and, on the other, on the improvement of gastrointestinal motility. Surprisingly, the widely used antacid drugs are among those which have been less well studied and show the lowest efficacy. Among the anti-secretory drugs, pirenzepine is approximately 25% more effective than placebo. H2-antagonists, the drugs which have been most closely studied both in terms of the number of trials and the size of the sample populations studied, produce contradictory results. However, a meta-analysis of the trials shows an overall 18% improvement in efficacy compared to placebo. The overall results of studies on prokinetic compounds are "good" in meta-analytical terms, with an improved efficacy of 50% compared to placebo. This is not necessarily due to the superiority of prokinetic compared to anti-secretory drugs and can be explained by the reduced placebo effect in trials using prokinetic drugs or a greater presence in the latter of dyspepsia which is physiopathologically correlated to motor discord. Among the future drugs still being studied, it is particularly worth mentioning fedotozine, a specific K opioid receptor agonist which appears to have provided extremely interesting results in preliminary studies. The role of barrier drugs, such as sucralfate and colloidal bismuth, continues to remain unclear and in particular the latter might be of increased use if evidence of a relationship between Helicobacter pylori and non-organic dyspepsia were reinforced; this relationship may in fact not exist in all dyspeptic patients but only in a subgroup. Lastly, the problem of the duration of pharmacological treatment still remains unsolved, as do the questions of whether longterm treatment should be conceived once acute symptoms have disappeared and whether it is possible to hypothesise differentiated pharmacological treatment depending on the clinical variants of functional dyspepsia which have been defined with greater attention over the course of the past decade.

Antisecretory agents, peptic secretion and serum pepsinogen in man.

Less attention has been devoted to the effects of antisecretory agents on pepsin secretion than to those on gastric acid secretion, particularly in human subjects. Moreover, comparison of the various trials is far from being simple and straightforward owing to the fact that the studies available present substantial variability in terms of types of subjects (controls, DU patients), gastric secretion (basal, stimulated), type of stimulation (pentagastrin, histamine, insulin, meals, sham feeding) antisecretory drug administration route (oral, i.v.) and considered parameters (concentration, output). This review of the published data reveals that all antisecretory agents reduce pepsin output, regardless of their sometimes very different mechanism of action. Despite this, there are differences in antisecretory effects according to the agent used to stimulate gastric secretion. Even within a single drug class (H2-antagonists, prostaglandins) there may be differences depending on the potency of the compound used.

The gastric acid conundrum in peptic ulcer.

According to the traditional view, gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanism of action antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents-thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing, yield contradictory clinical results; morning and bedtime single administration of H2-antagonists prove equiactive on ulcer healing, leading to a appraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby reapparently under-mining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the proton-pump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.

Drug treatment of functional dyspepsia. A meta-analysis of randomized controlled clinical trials.

The results of therapeutic trials in functional dyspepsia (FD), a frequently encountered condition, are contradictory. Our aim, then, was to produce a pooled estimate, or meta-analysis, of a series of short-term randomized placebo-controlled clinical trials on the pharmacological treatment of FD with antisecretory and gastrokinetic drugs. We retrieved trials for analysis purposes by consulting computerized data bases and by scanning published reviews, Current Contents, and references cited in the individual studies. We also requested bibliographical updates from the medical departments of the manufacturers of the drugs used in the various trials. Of 74 trials retrieved by these means, 23 proved eligible for meta-analysis on the basis of six selection criteria defined a priori. Results were expressed in terms of "therapeutic success" (TS), which includes "symptom-free patients," patients with "significant improvement in symptoms," "excellent results," and so on. The differences in TS rates between the various drugs and placebo were calculated in each trial as the algebraic difference together with the respective 95% confidence interval (95% C.I.); the pooling of results of all eligible trials was done using Cochran's weighted method. With antisecretory drugs, the mean difference in TS rates versus placebo was +20% (95% C.I.: 14-24%). The therapeutic gain for the respective antisecretory agents was 25% (95% C.I.: 14-36%) in the case of pirenzepine and 18% (95% C.I.: 12-24%) in the case of H2 antagonists. Meta-analysis of trials with gastrokinetic drugs also showed superior efficacy of these agents compared with placebo, with a mean difference in TS rates of +46% (95% C.I.: 40-52%).(ABSTRACT TRUNCATED AT 250 WORDS)

Oxmetidine in the short term treatment of active duodenal ulcer. A review and commentary.

Oxmetidine is an H2-antagonist like cimetidine containing an imidazole ring in its molecule, but differing from cimetidine in that it contains in the side-chain a substituted isocytosine moiety in place of the cyanoguanidine group. Nine controlled clinical trials are critically analysed in detail. The overall results show that the antiulcer activity of oxmetidine is not significantly different from that of cimetidine with mean healing rates by week 4 of 74.9% and 75.3%, respectively. Healing rates proved to be lower in smokers than in non-smokers in all trials but one. Satisfactory response as regards symptoms was obtained both with oxmetidine and cimetidine. A certain degree of variability with regard to the untoward effects was found, but in all cases failed to prove significant from the clinical point of view. However, a better definition of oxmetidine safety requires a study on a large number of patients and for a longer period.

Is ethanol metabolism affected by oral administration of cimetidine and ranitidine at therapeutic doses?

The aim of this study was to compare the ethanol serum concentration curve, the area under the curve and subjective response after acute ingestion of ethanol (red wine, 13 degrees proof, at a dose of 0.8 g/kg of ideal weight in 6 healthy volunteers with a mean habitual alcohol intake of 20 g/day. All the subjects underwent the test a total of three times, after pre-treatment with cimetidine (400 mg X 2/day/7 days) and ranitidine (150 mg X 2/day/7 days), respectively, and after receiving no pre-treatment. The wine was taken orally within the space of 15 min, four hours after taking a standard-weight ham sandwich. Blood samples were drawn at the following times: 0, 30, 60, 90, 120, 180, 240 and 360 minutes. The plasma ethanol curve of the subjects pre-treated with cimetidine lies above that of the subjects pre-treated with ranitidine, and largely coincides with the curve obtained in those who received no pre-treatment, with the exception of the initial hour-and-a-half, when the later show a slightly higher mean plasma concentration. The differences between the three treatment groups are merely arithmetical, but not statistical, with respect to peak plasma ethanol concentrations, time elapsing before peaking, and areas under the curves. These results are at variance with some published data suggesting a significant interaction of cimetidine with the metabolism of alcohol by way of interference either with the hepatic oxidative metabolizing enzymes, or with the activity of alcohol dehydrogenase.

Pirenzepine and exocrine secretions: a selective agent for gastric glands?

Nineteen healthy volunteers were studied to investigate whether or not muscarinic receptors of different exocrine glands could be distinguished from one another by the use of pirenzepine. A simultaneous evaluation of lacrimation, salivation and gastric secretion was carried out, bethanechol (80 micrograms/kg/hr) being used as a stimulant and pirenzepine (10 or 5 mg i.v.) as an inhibitor. Bethanechol increased salivation significantly and the volume of gastric juice, and non-significantly increased lacrimation and total acid output. Pirenzepine abolished the hypersecretion induced by bethanechol, and decreased the basal level of the exocrine secretions, to approximately the same extent. These experiments seem to demonstrate that if there is a difference among the muscarinic receptors of lacrimal, salivary and gastric oxyntic glands, pirenzepine is unable to discriminate them from one another, at least under the experimental conditions of this investigation.