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.

[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.

Extracorporeal shock wave lithotripsy (ESWL) of gallbladder stones: experience in Bolzano.

During a period of 24 months, 115 patients with symptomatic gallbladder stones (77 females, 38 males; median age 46 years, range 22-87) were treated by extracorporeal shock wave lithotripsy with a Lithostar Plus. Concomitant bile acid dissolution therapy (ursodeoxycholic acid + chenodeoxycholic acid 7.5 mg/kg/day each or tauroursodesoxycholic acid 5-10mg/kg/day) was administered until 3 months after total fragment clearance. Complete clearance of all fragments was obtained after 6, 9, 12, 18 and 24 months in, respectively, 30, 45, 51, 62 and 72%. Life table analysis of the subgroups showed significantly better clearance results in patients with fragments < 5mm at the first extracorporeal shock wave lithotripsy session (67%) than in patients with larger fragments (39%) (p < 0.01). Patients with solitary stones < 20mm cleared their fragments better (58%) at 12 months than those with multiple stones (49%), but the differences were not statistically significant. Stone recurrence was 6% at 1 year and was lower in patients with solitary stones (3%) than in those with multiple stones (12%). Major side effects consisted in 2 cases of mild acute pancreatits and 19% of biliary colics.

Chronic gastritis, intestinal metaplasia, dysplasia and Helicobacter pylori in gastric cancer: putting the pieces together.

Chronic gastritis may favour the development of gastric cancer more as a condition than as precancerous lesion. Since, in most cases, it is pathologically correlated with Helicobacter pylori infection, it is reasonable to postulate at least an indirect role for this organism in the pathogenesis of gastric cancer. H. pylori, however, is only one of the risk factors involved, in that additional factors (excess salt, cigarette smoking, deficiency of foodstuffs with an antioxidizing effect) may facilitate the malignant transformation of chronic atrophic gastritis into intestinal-type gastric cancer. Gastric carcinogenesis therefore presents itself as a multifactorial, multistage process, furthered by the occurrence of precancerous lesions which are usually interrelated (type-III intestinal metaplasia, severe dysplasia) and by functional alterations such as achlorhydria, which, though it is not enough in itself to cause gastric cancer, promotes abnormal intragastric bacterial development, a condition which may be followed by abnormal intragastric formation of cancerogenous nitroso compounds. The existence of a close correlation between both gastric cancer and H. pylori infection and low socio-economic and hygienic status of the population lends further strength to the hypothesis that an "H. pylori factor" is involved in gastric carcinogenesis. Consequently, to reduce the risk of gastric cancer, various strategies have been devised to prevent H. pylori infection (improvement in socio-environmental conditions, anti-H. pylori vaccine) and/or to eradicate the organism (by means of therapeutic regimens including antimicrobial agents, which, however, can be implemented only in patients who have not developed diffuse atrophy and/or dysplasia, in whom H. pylori may no longer be detectable). Definitive proof of the real extent of the relationship between H. pylori and gastric cancer and of the efficacy of therapeutic and preventive measures can be provided only by controlled trials in populations with a high prevalence of chronic non-atrophic gastritis which are difficult to organize.

[Helicobacter pylori and the treatment of gastric ulcer. Reflections and uncertainties]. / Helicobacter pylori y tratamiento de la úlcera gástrica. Reflexiones e incertidumbres.

The authors examine the relationship between Helicobacter pylori and gastric ulcer therapy, analyzing both the data suggesting that eradication of the organism renders the gastric mucosa less susceptible to development of gastric ulcer and the substantial body of evidence to the contrary. They review the results reported in clinical trials with colloidal bismuth subcitrate, antimicrobial agents (furazolidone), and combinations of antiulcer and antimicrobial agents (H2-antagonist + cefixime, H2-antagonist + metronidazole). Also analyzed is the relationship between Helicobacter pylori eradication and ulcer recurrence; only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of Helicobacter pylori facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

The need for long-term treatment of peptic ulcer.

Some 10% of the population in Western countries will suffer a duodenal ulcer or gastric ulcer at some time in their lives. Although there has been an improvement in the survival rate of patients with peptic ulcer haemorrhage, the mortality is still approximately 10%. There is evidence to suggest that peptic ulcer disease is a life-long condition and that ulcers remain active with an unchanged potential for complications such as haemorrhage and perforation. Over the past 15 years anti-ulcer drugs with different mechanisms of action have been developed, and their use results in complete healing of an ulcer in four to eight weeks. However, most patients experience recurrence of their peptic ulcer after discontinuation of the healing therapy. Studies of continuous H2-receptor antagonist therapy have shown that recurrence occurs less frequently than in untreated patients, is largely asymptomatic, and is rarely characterized by haemorrhagic complications. Limited data on therapy for the eradication of Helicobacter pylori suggest that this may be an alternative approach for selected patients. As protection afforded by H2-receptor antagonists remains undiminished over the course of several years and is also observed in ulcers which have bled in the past, the implementation of long-term management with these agents constitutes a rational policy.

Helicobacter pylori and gastric ulcer therapy: reflections and uncertainties.

The relationship between Helicobacter pylori (HP) and gastric ulcer therapy is examined by analyzing both the data that suggest that eradication of HP renders the gastric mucosa less susceptible to development of gastric ulcer as well as the substantial body of evidence that does not support this contention. The results reported in clinical trials with colloidal bismuth citrate, antimicrobial agents (furazolidone), and combinations of anti-ulcer and antimicrobial agents (H2-antagonist+cefixime, H2-antagonist+metronidazole) are reviewed. Also analyzed is the relationship between HP eradication and ulcer recurrence. Only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of HP facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

[No acid, no ulcer: such a simple axiom?]. / No ácido, no úlcera: un axioma tan simple?

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 mechanisms 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 administrations of H2-antagonists prove equiactive on ulcer healing, leading to a reappraisal 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 apparently undermining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the protonpump 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.

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.

Powerful gastric acid inhibition: when is it justified?

Peptic ulcers fail to heal in up to 10% of patients after 8 weeks of therapy with H2-receptor antagonists largely owing to the multifactorial pathogenesis of the disease. Site-protective agents may heal the ulcers in many, but not all, of these non-responders. In ulcers which prove particularly refractory to therapy, only powerful gastric acid inhibition of the type best achieved with omeprazole is capable of healing most, and sometimes even 100% of patients in the short term. Powerful inhibition of gastric acid secretion proves clinically advantageous, in terms both of symptom relief and endoscopic lesions, in severe reflux oesophagitis, characterized, as it is, by erosive and ulcerative lesions. Strong inhibition of acid secretion is, of course, also indicated in Zollinger-Ellison syndrome, the treatment of which has already been revolutionized by the use of H2-antagonists, usually given in very high doses, and appears to have made yet another step forward with the advent of omeprazole thanks to the particularly marked potency and duration of action of this benzimidazole derivative. Powerful inhibition of acid secretion thus seems possible both with high-dose H2-antagonists and, most notably, with omeprazole. Though fully justified in certain classic conditions such as refractory ulcer, erosive-ulcerative oesophagitis and Zollinger-Ellison syndrome, massive antisecretory blockade would not appear to be suitable for indiscriminate use, especially long-term.

Influence of ulcer healing agents on ulcer relapse after discontinuation of acute treatment: a pooled estimate of controlled clinical trials.

Whether or not the incidence of ulcer relapse varies according to the drug used to produce initial healing is a controversial matter. We tackled this problem using data from 15 eligible trials from 25 published controlled trials in patients followed up for six to 12 months. Pooled estimates of differences in ulcer relapse incidence between patients initially healed with H2-antagonists and patients initially healed with non-H2-antagonist drugs were calculated. The overall incidence of relapse in patients healed with comparator drugs is 11 percentage units lower at six and 12 months, than that observed in H2-antagonist-healed patients. The confidence intervals are +/- 8% at six months and +/- 7% at 12 months. These data suggest the existence of a different effect on relapse incidence for the entire class of comparator drugs taken as a whole, compared with H2-antagonists. On considering the non-H2-antagonists singly, this conclusion holds good only in the case of tripotassium dicitrato bismuthate.