Outcome of patients receiving photodynamic therapy for early esophageal cancer.

PURPOSE: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer. METHODS AND MATERIALS: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months). RESULTS: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy. CONCLUSION: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Gastric epithelial dysplasia: a prospective multicenter follow-up study from the Interdisciplinary Group on Gastric Epithelial Dysplasia.

To assess the evolution of gastric epithelial dysplasia (GED), a prospective multicenter study was based on a protocol of repeated endoscopies and biopsies. To date, 134 cases (0.4% of all patients endoscopically examined in the same period) have been diagnosed as having GED and 80 of those have had an "adequate" follow-up (at least three endoscopies). Mean follow-up time was 18 months. Gastric epithelial dysplasia was mild in 59% of cases, moderate in 25%, and severe in 10%. Six percent of the patients had lesions that were "indefinite for dysplasia." Chronic atrophic gastritis (40%), gastric ulcer (32%), gastrectomy (10%), and polyps (9%) were the most frequently associated lesions. The term "regression" was adopted for GED no longer detectable during follow-up and the term "progression" was used when more severe changes or cancer was detected. Mild GED regressed in 66% of cases, persisted in 15%, and progressed in 19% (three cases to moderate, one to severe, and five to cancer). Moderate GED regressed in 30% of patients, persisted in 30%, and progressed in 40% (one to severe GED and seven to cancer). Severe GED regressed in 12.5% of patients, persisted in 12.5%, and progressed to cancer in 75%. Of the five patients with lesions indefinite for dysplasia, two had no dysplastic changes at follow-up and three had cancer diagnosed. Ten of 21 cases of cancer (48%) were at the early stage. The diagnosis was reached within the first year of follow-up in 14 cases and after 1 year in seven (13 to 39 months). Fifteen of 21 cases of cancer were diagnosed in gastric ulcer patients. In conclusion, GED is an infrequent finding and its biologically neoplastic significance is confirmed by the results of the follow-up study: (1) in its mild form, it tends to regress but adequate subsequent check-ups are mandatory as it may associate with or evolve as cancer; (2) patients with moderate GED require strict follow-up since the lesion shows a higher cancer risk; (3) surgery is indicated for severe GED because gastric cancer develops in 75% of cases; and (4) patients with lesions indefinite for dysplasia should immediately undergo repeat endoscopy and biopsy. Such an approach allows gastric cancer to be detected at an early stage in a much higher percentage of cases than may be expected.

How do general practitioners rate their relationship with gastroenterologists?

BACKGROUND: Relations between general practitioners and the hospital consultants are often considered difficult, and occasionally generate conflicts, potentially affecting the patient management and healthcare system organisation. These views, however, have partly been contradicted by structured surveys and qualitative studies. AIMS: We conducted a survey on the general practitioners' opinions regarding their relations with the gastroenterological-endoscopy services in order to explore current attitudes, any negative aspects and assess scope for improvement. SUBJECTS AND METHODS: Structured questionnaires were sent to 221 general practitioners in the Veneto region of Italy; the questionnaire was based on 26 questions concerning their subjective relations with the gastroenterologists, expertise in the gastroenterological problems and perceived efficiency of gastroenterological services. RESULTS: As many as 106 doctors answered the postal questionnaire (mean: 15 per province; range 5-20). Responses to the structured questions totalled to 2,339 items, out of which 1,234 (53%) presented positive responses, particularly with regard to admissions' management and the adequacy of referral reports. Many general practitioners reported of their participation in the meetings on gastroenterological problems. Homecare referrals were limited in number, even for the patients with tube feeding. CONCLUSIONS: Relations between the general practitioners in Veneto and local gastroenterological services were generally good, possibly reflecting the well-developed outreach network. This liaison could be further improved via closer interrelations based not only on the patient referrals but also on the professional and information exchange to promote successful practice.

Qualitative assessment of von Willebrand factor (vWF) in cirrhotics following repeated doses of desmopressin acetate.

Qualitative abnormalities in von Willebrand Factor (vWF) in patients with cirrhosis have been little studied with contrasting results. We used crossed immunoelectrophoresis (2-DIE) and multimeric analysis of vWF in eight patients with stable hepatic cirrhosis to evaluate abnormalities in vWF before and 1 h following intravenous administration of three doses of desmopressin acetate (0.3 micrograms/kg) given at baseline, 4 and 24 h. We thought that qualitative abnormalities might be more easily detected following desmopressin as this is known to release vWF from storage sites. There was an increased electrophoretic mobility on 2-DIE in all patients with no change following desmopressin. The multimeric analysis did not show an increase in lower molecular weight multimers, but showed a statistically significant increase in higher molecular weight multimers following desmopressin (P less than 0.02). These results suggest that the vWF of cirrhotics has an abnormal charge (not altered by release following desmopressin) which would explain the increased electrophoretic mobility on 2-DIE with a normal pattern of lower molecular weight multimers using multimeric analysis.

Gastric epithelial dysplasia and sulphomucin-type intestinal metaplasia.

The HID-AB histologic staining technique, which distinguishes sulphomucin from sialomucin types of intestinal metaplasia, was employed in endoscopic gastric mucosal biopsies to evaluate their frequency of association with epithelial dysplasia. Sulphomucin-type intestinal metaplasia was found in 33% of the cases under observation; moderate or severe dysplasia was only associated with this type of intestinal metaplasia. Its precancerous significance can be ascertained only by means of prospective studies.

[Intragastric pH determination as a screening test in the diagnosis of chronic atrophic gastritis]. / Il pH intragastrico come test di screening per la diagnosi di gastrite cronica atrofica.

A simple routine endoscopic screening test has been sought for the diagnosis of chronic atrophic gastritis. An endoscopic-bioptic study was therefore carried out on 850 subjects presenting consecutively at a Digestive Endoscopy Department with dyspeptic-pain symptomatology. In a first sample of 389 patients, 2 biopsies of the gastric body and 2 of the gastric antrum were carried out, independently of the endoscopically documented macroscopic picture. Atrophic changes were in this way encountered in 65 patients (16.7%). In a second group of 461 patients, intragastric pH was determined extemporaneously during endoscopy. pH was = or greater than the chosen threshold value (3.5) in 117 patients and less than this value in 344. In all subjects with pH greater than 3.5 and, by comparison, in 130 with pH less than 3.5 biopsy was carried out on the gastric mucosa, 2 biopsies of the body and 2 of the antrum. Using this approach it was possible to determine the presence of atrophic changes in the gastric mucosa in 57 of 117 (48%) and in 25 of 130 (20%) respectively. In total, chronic atrophic gastritis was diagnosed in 83 of 461 subjects (18%). This percentage is comparable to that observed in the frequency of chronic atrophic gastritis using the more demanding and less selective test of bioptic sampling indiscriminately for all patient. So, the straight-forward determination of intragastric pH in a sample of gastric juice taken during digestive endoscopy would appear to meet the criteria demanded for a screening test and its wider use is recommended in routine endoscopic practice.

[Methodological aspects of gastric acid examination]. / Aspetti metodologici del sondaggio gastrico.

The aim of the present work was to study gastric acid secretion in control subjects and in gastric and duodenal ulcer patients and to evaluate sex, age, body weight, blood group, cigarette smoking and the intake of H2-blockers in the 24 hours preceding gastric acid analysis. The results obtained seem to indicate that 6 micrograms/kg b.w./i.m. Pentagastrin is the best stimulus and that basal secretion may be assessed in thirty minutes, without altering the BAO value. Factors such as cigarette-smoking and H2-blockers intake on the one hand and body weight and male sex on the other influence gastric juice output and should therefore be considered in interpreting the results.

The risk of gastric dysplasia in medical long-term treatment of peptic ulcer disease.

There have been recent findings of gastric cancer in patients treated with cimetidine but too soon after treatment for that drug to have had a pathogenetic role. Ranitidine has been shown to induce slight changes in the gastric mucosa. In 117 patients with gastric ulcer followed-up in some cases for 24 months, five cases of cancer were detected, one after more than a year of follow-up. The numbers were too small to allow any conclusion to be drawn regarding relationships with medication. No significant differences in incidence of gastric epithelial dysplasia between control patients and patients treated with cimetidine or ranitidine were found. No dysplastic lesions were seen during a brief follow-up of 19 duodenal ulcer patients and a few gastric ulcer patients treated with pirenzepine but the data is too limited to allow conclusions to be drawn.

Two-stage endoscopic removal of a foreign body from the common bile duct.

We describe the application of a new two-stage endoscopic procedure for removal of a retained stent in the common bile duct (Type 1 foreign body in Ban's classification). The technique involves sphincterotomy and placement of the endoprosthesis.

Adult "idiopathic" extrahepatic venous thrombosis. Importance of putative "latent" myeloproliferative disorders and comparison with cases with known etiology.

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a "latent" myeloproliferative disorder has been reported in adults with "idiopathic" EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The "idiopathic" group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17-70) with a median follow up of 96 months (19-372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.

Guidelines on the management of H.pylori in primary care: development of an implementation strategy.

BACKGROUND: Clinical guideline programmes as being developed in many European countries contribute to quality of care in general practice. The applicability of multicountry guidelines will depend on country-specific circumstances. Implementation programmes are required for optimal compliance with guidelines. OBJECTIVE: In order to achieve optimal follow-up of the European Society for Primary Care Gastroenterology (ESPCG) Helicobacter pylori guidelines in general practice, we analysed factors that might obstruct compliance at national level, and integrated this in implementation programmes. METHOD: Discussion groups in eight participating countries reviewed epidemiological characteristics and diagnostic and therapeutic resources that would hinder applicability. The groups also indicated potential constraints to optimal compliance and developed a national implementation programme. RESULTS: Helicobacter pylori infection rates and peptic ulcer incidence vary widely across Europe, as do the availability, access and reimbursement of diagnostic test facilities for H.pylori Minor adaptation of the ESPCG guidelines is required in some countries. Implementation programmes have been developed and partially carried out in all countries. CONCLUSION: A pan-European approach to H.pylori guideline development should result in a framework of best practice into which nationally specific details can be incorporated, thus guaranteeing optimal follow-up of the guidelines and true improvement of dyspepsia management in primary care.

A predictive model for failure to control bleeding during acute variceal haemorrhage.

BACKGROUND/AIMS: Variceal bleeding is a frequent complication of cirrhosis and is associated with a high risk of early rebleeding. In patients with peptic ulcers, continued bleeding or early rebleeding are risk factors for mortality and can be predicted by statistical models; however, no such models exist for acute variceal bleeding. METHODS: We prospectively evaluated failure to control bleeding in 695 consecutive patients with cirrhosis, admitted for haematemesis and/or melaena. Criteria were defined for failure to control bleeding, which comprised both continued bleeding or early rebleeding within 5 days of admission. There were 2 sequential groups of patients: (i) those with variceal bleeding initially treated with blood transfusion and vasoactive drugs, and if these failed followed by sclerotherapy (n = 385); (ii) those with variceal bleeding treated with injection sclerotherapy at diagnostic endoscopy (n = 144). The third group was those with bleeding from other sources related to portal hypertension (n = 166). RESULTS: Failure to control bleeding was noted in 169 (44%) patients in group 1, 55 (38%) in group 2 and 44 (25%) in group 3. Twenty variables that were evaluable within 6 h of admission, pertaining to severity of bleeding, severity of type of liver disease, mode of admission, and time of diagnostic endoscopy, were entered into a multivariate Cox model. Independent predictors of early rebleeding in group 1 were: active bleeding at endoscopy (irrespective of interval from admission) (p<0.0001), encephalopathy (p = 0.007), platelet count (p = 0.002), history of alcoholism (p = 0.002), presentation with haematemesis (p = 0.02), log urea (p = 0.03) and (shorter) interval to admission (p = 0.007). The variables predictive of 30-day mortality were: early bleeding (p<0.0007), bilirubin (p = 0.0006), encephalopathy (p<0.0001), (shorter) interval to admission (p<0.0001), and log urea (p = 0.004); a model based on these variables was also a good predictor of mortality in the other 2 groups. However, the model derived from group 1 for failure to control variceal bleeding was different in group 2, despite similar patient characteristics and a similar failure rate (following a single injection). This could suggest that sclerotherapy may induce bleeding in some patients independently of the baseline risk for failure to control bleeding. CONCLUSIONS: In cirrhotic patients who present with haematemesis or melaena, active variceal bleeding at diagnostic endoscopy is predictive of failure to control bleeding (continued bleeding or early rebleeding within 5 days of admission), and this failure is predictive of 30-day mortality.

Is mild gastric epithelial dysplasia an indication for follow-up?

We evaluated the changes over 1-55 months in mild gastric epithelial dysplasia (a relatively frequent, but not widely studied histological lesion) in 20 patients (11 with benign gastric ulcer, eight with chronic gastritis, and one after Billroth 2 operation), in order to ascertain whether to follow-up such patients in the future. Regression of the lesion was documented in 13 (65%), and no change in six (30%). Progression from mild to moderate dysplasia occurred in only one patient (5%). As mild dysplasia regresses or remains unchanged in most patients, at least over the short-term, specific follow-up is probably unnecessary. Nevertheless, a rational program of monitoring the associated precancerous conditions is in order.

Perendoscopic gastric pH determination. Simple method for increasing accuracy in diagnosing chronic atrophic gastritis.

The endoscopic diagnosis of chronic atrophic gastritis is often underestimated, and most of the procedures adopted to increase diagnostic accuracy are time consuming and complex. In this study, we evaluated the usefulness of the determination of gastric juice pH by means of litmus paper. Values obtained by this method correlate well with gastric acid secretory capacity as measured by gastric acid analysis (r = -0.64, p less than 0.001) and are not affected by the presence of bile. Gastric juice pH determination increases sensitivity and other diagnostic parameters such as performance index (Youden J test), positive predictive value, and post-test probability difference by 50%. Furthermore, the negative predictive value is very high, the probability of missing a patient with chronic atrophic gastritis with this simple method being 2% for fundic and 15% for antral atrophic change. We conclude that gastric juice pH determination, which substantially increases diagnostic accuracy and is very simple to perform, should be routinely adopted.

Are biopsy forceps helpful in the endoscopic evaluation of ulcer diameter?

A hand-made papier-mâché stomach model with hollowed-out ulcers was employed for evaluating the accuracy in estimating ulcer diameters by means of endoscopy. The opened biopsy forceps were also used as a reference marker. Ten endoscopists with various degrees of experience were involved in the study. All the endoscopists underestimated the ulcer diameters; the use of the forceps, resulted in an improvement, in particular in the case of the comparatively inexperienced endoscopists. A stomach model may be helpful in the subjective assessment of the endoscopists' ability to estimate ulcer size.

Esophageal staple transection as a salvage procedure after failure of acute injection sclerotherapy.

It is not clear which therapy should be used in patients with bleeding esophageal varices that are not controlled by emergency sclerotherapy. This is a high-risk group with reported mortality rates of between 70% and 90%. We report our 7-yr experience with staple transection of the esophagus in this patient group. Of 168 patients (280 bleeding episodes) treated with sclerotherapy, 22 had emergency staple transection for failure to control bleeding. Bleeding was controlled in 20 patients (90%), and 10 patients (45%) survived to leave the hospital, including 4 of 10 patients (40%) with Pugh grade C liver disease. We suggest that emergency staple transection is an effective salvage treatment for this high-risk group.

Congestive gastropathy and Helicobacter pylori: an endoscopic and morphometric study.

Congestive gastropathy is a frequent cause of upper gastrointestinal haemorrhage in patients with portal hypertension. The pathogenesis is thought to involve venous congestion with gastric mucosal capillary dilatation. We studied the relation between gastric mucosal capillary dilatation, measured morphometrically, and endoscopic appearances in 74 patients with portal hypertension and 20 control subjects. We also investigated the frequency of gastric colonisation with Helicobacter pylori. Mucosal capillaries in patients were significantly dilated compared with control subjects (p less than 0.001) but the degree of dilatation was not related to the severity of the endoscopic appearances. H pylori was identified in 19 of 74 (26%) patients but was not related to the severity of the endoscopic appearances. These results suggest that other factors in addition to mucosal venous and capillary congestion are important in the pathogenesis of endoscopic congestive gastropathy and that gastric colonisation with H pylori is unlikely to be one of these factors.

Gastric ulcer and stomach aging: pathophysiology and clinical implications.

138 consecutive patients with endoscopically and histologically confirmed benign gastric ulcer were investigated in order to evaluate the relationship between aging and parameters relating to gastric ulcer pathophysiology and natural history: prevalence in dyspeptic patients referred to an endoscopic unit, recurrences, gastric acid secretory capacity, peptic activity, incidence of precancerous and neoplastic changes. On the basis of our results, different populations of gastric ulcer patients seem to be identifiable: (1) young patients (aged under 40), with low prevalence and recurrence rates, with acid capacity above normal range, high peptic activity and no risk for precancerous or neoplastic changes, (2) middleaged subjects (41-50), with high prevalence and recurrence rates, high peptic activity and acid activity within the normal range, atrophic gastritis, intestinal metaplasia, dysplasia and low incidence of cancer, and (3) elderly patients (aged over 50), with lower prevalence and recurrence rates, frequent association with chronic atrophic gastritis, impaired acid and peptic secretion, in whom one may observe either an association of the ulceration with cancer or evolution of dysplasia into neoplasia. These observations confirm that elderly and middle-aged gastric ulcer patients should undergo routine follow-up, and that pathophysiological data should be taken into account before deciding upon antiulcer therapy.

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.