Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats.

BACKGROUND: This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats. STUDY DESIGN: One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. RESULTS: Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I. CONCLUSIONS: Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.

Evidence for intestinal oxidative stress in patients with obstructive jaundice.

BACKGROUND: Obstructive jaundice results in failure of the intestinal barrier with consequent systemic endotoxemia associated with septic complications. We have recently shown that gut barrier failure in experimental obstructive jaundice is associated with high intestinal oxidative stress. This study was undertaken to investigate whether oxidative alterations occur in the intestinal mucosa of patients with obstructive jaundice. PATIENTS AND METHODS: Fifteen patients with malignant biliary obstruction and no signs of cholangitis and 15 control patients were subjected to duodenal biopsy to assess intestinal oxidative stress, estimated by lipid peroxidation (malondialdehyde - MDA) and glutathione redox state [reduced glutathione (GSH), glutathione disulphide (GSSG) and GSH/GSSG ratio]. In addition, mucosal biopsies were examined histologically and intestinal mucosal protein content was determined biochemically as an index of intestinal trophic state. RESULTS: Patients with obstructive jaundice presented high levels of intestinal oxidative stress, with significantly increased lipid peroxidation (P < 0.001). Glutathione redox state was also suggestive of high intestinal oxidative stress in jaundiced patients, indicated by significantly decreased GSH (P = 0.001) and GSH/GSSG ratio (P = 0.006) and increased GSSG (P = 0.026). Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in obstructive jaundice, whereas duodenal architecture remained intact and epithelial continuity was retained. Duodenal mucosa was atrophic in jaundiced patients as indicated by a significant reduction of mucosal protein content compared with controls (P = 0.001). Among oxidative stress parameters, intestinal GSH exhibited a significant positive correlation with mucosal protein content (r = 0.588, P = 0.021). CONCLUSIONS: Obstructive jaundice in humans induces intestinal oxidative stress, which may be a key factor contributing to intestinal barrier failure and the development of septic complications in this patient population.

Pre-emptive analgesia: how important is it in clinical reality?

Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. In experimental studies, preinjury (e.g. pre-emptive) neural blockade using local anaesthetics or opioids has been shown to prevent or to reduce postinjury sensitization of the central nervous system, while similar techniques applied after the injury had less or no effect. Several clinical studies have evaluated possible pre-emptive analgesic effects by administering prior to surgery a variety of analgesic drugs both systemically or epidurally. These treatment modalities were compared to the same treatment following surgery or to control groups not given such treatment. In general, the results from these studies have been disappointing, although some clinical studies have confirmed the impressive results from animal studies. The present paper discusses deficiencies in study design of clinical trials, since the question regarding the effectiveness of pre-emptive analgesic regimens lies not so much in the timing of analgesic administration (e.g. preinjury vs. postinjury treatment), but in the effective prevention of altered central sensitization. Recent evidence suggests that administration of analgesics in order to effectively pre-empt postoperative pain should start before surgery and furthermore, this treatment should be extended into the early postoperative period.

Preoperative staging and evaluation of resectability in pancreatic ductal adenocarcinoma.

BACKGROUND: Cancer of the pancreas is a common disease, but the large majority of patients have tumours that are irresectable at the time of diagnosis. Moreover, patients whose tumours are clearly beyond surgical cure are best treated non-operatively, if possible, by relief of biliary obstruction and percutaneous biopsy to confirm the diagnosis and then consideration of oncological treatment, notably chemotherapy. These facts underline the importance of a standard protocol for the preoperative determination of operability (is it worth operating?) and resectability (is there a chance that the tumour can be removed?). Recent years have seen the advent of many new techniques, both radiological and endoscopic, for the diagnosis and staging of pancreatic cancer. It would be impracticable in time and cost to submit every patient to every test. This review will evaluate the available techniques and offer a possible algorithm for use in routine clinical practice. DISCUSSION: In deciding whether to operate with a view to resecting a pancreatic cancer, the surgeon must take into account factors related to the patient, the tumour and the institution and team entrusted with the patient's care. Patient-related factors include age, general health, pain and the presence or absence of malnutrition and an acute phase inflammatory response. Tumour-related factors include tumour size and evidence of spread, whether to adjacent organs (notably major blood vessels) or further afield. Hospital-related factors chiefly concern the volume of pancreatic cancer treated and thus the experience of the whole team. Determination of resectability is heavily dependent upon detailed imaging. Nowadays conventional ultrasonography can be supplemented by endoscopic, laparoscopic and intra-operative techniques. Computed tomography (CT) remains the single most useful staging modality, but MRI continues to improve. PET scanning may demonstrate unsuspected metastases and likewise laparoscopy. Diagnostic cholangiography can be performed more easily by MR techniques than by endoscopy, but ERCP is still valuable for preoperative biliary decompression in appropriate patients. The role of angiography has declined. Percutaneous biopsy and peritoneal cytology are not usually required in patients with an apparently resectable tumour. The prognostic value of tumour marker levels and bone marrow biopsy is yet to be established. Preoperative chemotherapy or chemoradiation may have a role in down-staging an irresectable tumour sufficiently to render it resectable. Selective use of diagnostic laparoscopy staging is potentially helpful in determination of resectability. Laparotomy remains the definitive method for determining the resectability of pancreatic cancer, with or without portal vein resection, and should be undertaken in suitable patients without clear-cut evidence of irresectability.

Improved techniques in the surgical treatment of hepatic hydatidosis.

We evaluated 64 patients with hepatic hydatidosis who were treated during 1982 to 1988. The main clinical manifestations were epigastric pain (84 per cent), hepatomegaly (31 per cent), fever (30 per cent) and jaundice (25 per cent). Five patients were asymptomatic. All diagnoses were established by ultrasonography and computed tomography, or both (sensitivity rates of 95 and 93 per cent, respectively). Treatment was exclusively surgical and there were no deaths. In the five patients in group 1, total cystectomy was done without morbidity. The 19 patients in group 2 underwent a limited capsectomy, evacuation of the cyst, omentoplasty, suturing of the biliary communications and drainage of the residual cavity, with a rate of morbidity of 42 per cent. In the 40 patients in group 3, a wide capsectomy and unroofing of the cyst were done, the contents were removed, the cavity edges were hemostatically oversewn and the residual hepatic cavity was drained through a high vacuum, closed drainage system. Omentoplasty was not routinely done. With this technique, the rate of morbidity was reduced to 2.5 per cent. Of 64 patients, 32 were observed for an average of 42 months with a recurrence rate of 9 per cent. Because of the low rate of postoperative morbidity, recurrence and the shorter period of hospitalization, the surgical technique used in group 3 seems to be an efficient method for hepatic hydatidosis.

Nonabsorbable antibiotics reduce bacterial and endotoxin translocation in hepatectomised rats.

There is increasing evidence that septic complications, occurring after major hepatectomies, may be caused by gram negative bacteria, translocating from the gut. We investigated in rats, the effect of extended hepatectomy on the structure and morphology of the intestinal mucosa as well as on the translocation of intestinal bacteria and endotoxins. We also examined the effect of nonabsorbable antibiotics on reducing the intestinal flora and consequently the phenomenon of translocation by administering neomycin sulphate and cefazoline. Hepatectomy was found to increase translocation, while administration of nonabsorbable antibiotics decreased it significantly. In addition, hepatectomy increased the aerobic cecal bacterial population, which normalised in the group receiving antibiotics. Among the histological parameters evaluated, villus height demonstrated a significant reduction after hepatectomy, while the number of villi per cm and the number of mitoses per crypt, remained unchanged. Our results indicate that administration of nonabsorbable antibiotics presents a positive effect on bacterial and endotoxin translocation after extended hepatectomy, and this may be related to reduction of colonic bacterial load as an intraluminal effect of antibiotics.

Seasonality in the prevalence of acute upper gastrointestinal bleeding.

The seasonal fluctuations of acute upper gastrointestinal bleeding treated from 1991 to 1996 in Patras, Greece, were analyzed retrospectively. During that period, 1992 patients with acute upper gastrointestinal bleeding were admitted to our hospital. After patients who were not residents of the region served by our hospital were excluded, the remaining 1879 cases were reviewed. We observed seasonal fluctuation with low prevalence in winter and an increase in spring and autumn with two peaks in April and October (p < 0.00001). The seasonal prevalence parallels that of duodenal ulcer bleeding, which follows a similar fluctuation (p < 0.00001). Bleeding due to gastric ulcers or other causes presented no periodicity. Seasonal fluctuation, both in total numbers of upper gastrointestinal bleeding and in duodenal ulcer bleeding, was statistically significant only in patients not receiving nonsteroidal anti-inflammatory drugs (p < 0.00001). We conclude that upper gastrointestinal bleeding shows a seasonal fluctuation parallel to duodenal ulcer bleeding and is not related to nonsteroidal anti-inflammatory drugs. The seasonal pattern supports the traditional view of duodenal ulcer exacerbations.

Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats.

AIM: An important factor that promotes bacterial and endotoxin translocation in obstructive jaundice is intestinal injury that causes increased permeability. However, little is known of the submicroscopic biochemical events leading to defects of the intestinal barrier. This study was undertaken to investigate the effect of experimental obstructive jaundice on intestinal lipid peroxidation, protein oxidation and thiol redox state. METHODS: Rats were randomly divided into controls, sham operated and bile duct ligated (BDL). After 10 days, intestinal barrier function was assessed by measuring endotoxin in portal and aortic blood. Tissue samples from the terminal ileum were examined histologically and morphometrically, while other samples were homogenized for the determination of lipid peroxidation, protein oxidation and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulphides (NPSSR), protein thiols (PSH) and protein disulphides (PSSP)]. RESULTS: Obstructive jaundice compromised intestinal barrier function leading to significant portal and systemic endotoxaemia. The intestinal mucosa in jaundiced rats was atrophic with significantly decreased villous density and total mucosal thickness. Determination of biochemical parameters of oxidative stress in the intestine showed increased lipid peroxidation and protein oxidation in BDL-rats. Thiol redox state revealed the presence of intestinal oxidative stress in jaundiced rats, indicated by a decrease in GSH and increased GSSG, NPSSR and PSSP. CONCLUSIONS: This study shows that experimental obstructive jaundice induces intestinal oxidative stress, which may be a key factor contributing to intestinal injury and leading to endotoxin translocation.

Peritoneal echinococcosis.

Peritoneal echinococcosis is rare, even in areas where hydatid disease is endemic. Although the liver and lungs are the organs most commonly involved, peritoneal echinococcosis, either primary or secondary, represents an uncommon but significant manifestation of the disease. We reviewed the medical records of 121 patients with abdominal echinococcosis operated on in our department over the past 12 years. Peritoneal echinococcosis was found in 17 patients, usually combined with liver disease. The presenting symptoms were mostly atypical, and a few cases were discovered accidentally during routine follow-up after operations for hepatic echinococcosis. Surgery remains the best curative or palliative treatment for peritoneal echinococcosis, although anthelmintics can be an effective alternative for the treatment of small and asymptomatic cysts.

Conservative surgery in the treatment of hepatic hydatidosis.

OBJECTIVE: To examine the morbidity, mortality and recurrence rate after a modified conservative operation in the treatment of hepatic hydatidosis. DESIGN: Prospective open study. SETTING: University hospital, Greece. SUBJECTS: 67 Consecutive patients with hepatic hydatidosis, operated on between 1985 and 1990. INTERVENTION: The liver was mobilised and abdominal cavity isolated with pads soaked in 15% saline solution. Hydatid fluid was aspirated from the cysts which were widely deroofed, sterilised with 15% saline, and then oversewn with a braided absorbable suture. Drains were left in place and a third of patients also had omentoplasty (n = 22). MAIN OUTCOME MEASURES: Morbidity, mortality and recurrence rate. RESULTS: One patient died (1%), 4 developed complications (6%), and there were 3 recurrences (6%). It made no difference whether an omentoplasty was added or not. CONCLUSION: Conservative surgery achieves satisfactory results in the treatment of hepatic hydatidosis.

Predictors of hemostatic failure after adrenaline injection in patients with peptic ulcers with non-bleeding visible vessel.

BACKGROUND: Non-bleeding visible vessel (NBVV) in patients with bleeding peptic ulcer is associated with a high risk of rebleeding. The aim of this study was to define factors associated with failure of endoscopic hemostasis and rebleeding in patients with NBVV. METHODS: Clinical and endoscopic parameters related to failure of endoscopic hemostasis with adrenaline in 191 bleeding peptic ulcer patients with NBVV were evaluated. RESULTS: Endoscopic hemostasis was permanently successful in 154 patients (80.6%). Emergency surgical hemostasis for rebleeding was required in 37 patients (19.4%). Univariate analysis showed that therapeutic failure was significantly related to the presence of shock on admission (P=0.003), posterior duodenal ulcers (P=0.001), peptic ulcer history (P=0.001), previous peptic ulcer bleeding (P=0.002), or lack of history of non-steroidal anti-inflammatory drugs consumption, when compared to use of such drugs (P=0.04). Patients where therapy failed had lower hemoglobin levels at admission (7.8+/-1.9 g/dL versus 10+/-2.4 g/dL, P=0.005). In a multivariate analysis low hemoglobin (P<0.001) as well as history of previous peptic ulcer bleeding (P=0.002) and posterior duodenal ulcers (P=0.001) were negative predictors. Using the mean value of hemoglobin as the cut-off point, it is noteworthy that only 2 out of 81 patients (2.5%) who had none of these predictive factors required emergency surgical hemostasis, whereas 34 out of 110 patients (30.9%) with at least one predictive factor required emergency surgery. CONCLUSION: It is possible, by employing specific characteristics, to define a subgroup of high-risk patients for rebleeding in patients with NBVV despite therapeutic endoscopy and thus candidates for a complementary endoscopic method of hemostasis or emergency surgical intervention.

The effect of endoscopic injection therapy on the clinical outcome of patients with benign peptic ulcer bleeding.

BACKGROUND: Our aim was to investigate the effect of endoscopic injection therapy on the clinical outcome of patients with benign peptic ulcer bleeding. METHODS: In this study 1203 patients admitted with peptic ulcer bleeding over a 5-year period (January 1987 to April 1991) before endoscopic therapy and 1028 patients admitted with peptic ulcer bleeding after introduction of endoscopic therapy (May 1991 to March 1996) were assessed. Endoscopic therapy was performed in all patients with active bleeding or non-bleeding visible vessels during emergency endoscopy with injection of adrenaline, 1:10,000 in 0.9% saline. RESULTS: The introduction of injection therapy was associated with a reduction in transfusion requirements (from 5.1 +/- 2.6 to 3.4 +/- 1.8 units), hospitalization days (from 10.8 +/- 6.5 to 7.8 +/- 5.1 days), surgical interventions (from 50.6% to 23.6%), and mortality (from 12.9% to 4.6%) in patients with active bleeding or non-bleeding visible vessels (P < 0.05) but remained unchanged in the rest. Patients with gastric ulcer had a more pronounced reduction in emergency surgical haemostasis and mortality than patients with duodenal ulcer. There were no deaths or procedure-related complications. CONCLUSION: Endoscopic injection therapy with adrenaline/saline is a simple, low-cost, and safe method that improves the clinical outcome and reduces the mortality in patients with peptic ulcer bleeding.

Evaluation of the effects of autotransfusion of unprocessed blood on hemodynamics and oxygen transport in anesthetized pigs.

OBJECTIVE: To examine the hemodynamic effects and the oxygen transport pattern of autotransfusion of unprocessed blood on hemodynamics and oxygen transportation. DESIGN: Prospective, observational study. SETTING: Research laboratory of a university medical center. SUBJECTS: Six healthy, domestic pigs (20 - 33 kg). INTERVENTIONS: A left thoracotomy was performed and a 5-mm incision was created in the descending aorta, resulting in a controlled hemorrhage of 30 mL/kg (approximately 40% of blood volume) into the thoracic cavity over a 45-min time period. During that period, mean arterial pressure (MAP) was maintained slightly > 50 mm Hg, using intravenous lactated Ringers' solution. The blood sample was collected from the open thorax with compresses soaked in citric acid solution and then extracted by manual squeezing, filtered through several layers of gauzes, and stored in glass bottles. Repeat measurements were performed after hemorrhage, after retransfusion of the harvested blood, and thereafter every 15 mins up to 60 mins. The animals were supported for 2 more hrs and were observed for the following 48 hrs. MEASUREMENTS AND MAIN RESULTS: All animals survived and were in good condition 48 hrs after the experimental hemorrhage. The circulatory and oxygen transport response at the end of hemorrhage and concomitant maintenance of blood pressure at > 50 mm Hg resulted in: significant reductions of cardiac index, MAP, and oxygen transport (DO2) (46%, 50%, and 64% reductions, respectively, p < .01, in an increase of heart rate (HR) (+21%, not significant), pulmonary vascular resistance index (+112%, p < .05), and oxygen extraction (+105%, p < .01), as well as in a nonsignificant decrease of systemic vascular resistance index (-8%). After autotransfusion, the basic hemodynamic variables, MAP and HR were corrected, remaining near baseline (not significant) afterward. Cardiac index and DO2 increased after autotransfusion, but remained below the baseline until the end of the study protocol (p < .05). A significant increase was noticed for pulmonary arterial pressure and pulmonary vascular resistance index immediately after autotransfusion (p < .01). These values were corrected in part after 15 to 30 mins, but remained higher throughout the observaton period compared with baseline (29.5% and 89.8%, respectively, p < .05). The recently introduced relationship between cardiac index and oxygen extraction has been proposed to avoid problems of mathematical coupling between oxygen consumption and DO2 measurements. This relationship followed a similar course in all experiments throughout each phase. A shift downward and to the right represented the endpoint of the hemorrhagic phase. After autotransfusion, a shift toward baseline was noticed. Prothrombin time and partial thromboplastin time remained unchanged after autotransfusion. Free hemoglobin concentrations increased immediately after autotransfusion (+33%, p < .05), but returned to baseline values 48 hrs later. Histologic examination showed no changes in the examined organs. CONCLUSIONS: Reinfusion of large amounts of unprocessed blood (up to 40% of blood volume), collected with compresses from a noncontaminated surgical field is a cheap method, which may be of potential benefit in trauma patients, when more sophisticated autotransfusion devices are lacking. In the present study, this method resulted in transient but significant hemodynamic changes in the pulmonary circulation. Impairment of oxygen transport was noticed after the end of hemorrhage, but this impairment cannot be attributed to the autotransfusion technique alone, but also to factors such as hemorrhagic shock, surgical trauma, etc.

Pylorus-preserving total pancreatectomy. Early and late results.

BACKGROUND/AIMS: Preservation of the pylorus is an accepted alternative procedure to the classical Whipple operation for pancreatic head resection but data describing its value for total pancreatectomy are sparse. METHODS: A prospective analysis of 22 total pancreatectomies performed in a consecutive series of 436 pancreatic resections from 1.11.93 to 1.5.99. RESULTS: 11 patients underwent total pancreatectomy with preservation of the pylorus. Histopathological examination revealed pancreatic adenocarcinoma in 16 cases and duodenal adenocarcinoma in 1 patient, 5 patients had other types of pancreatic neoplasm. In-hospital mortality was 4.5% (n = 1), cumulative morbidity was 59% and reoperations were performed in 9.1% of cases (n = 2). Median follow-up was 37 months (range 5-66). 62% of patients (n = 13) developed tumor recurrence and 13 patients died during the follow-up period with 10 deaths being cancer related. There was no difference concerning postoperative and follow-up morbidity of survival between patients undergoing pylorus-preserving total pancreatectomy or pancreatectomy with gastrectomy. However, postoperative body weight was increased 3, 6, 9 and 12 months following preservation of the pylorus. CONCLUSION: Total pancreatectomy with preservation of the pylorus is a feasible type of resection for all types of pancreatic or ampullary tumors, which shows a similar morbidity and long-term survival but improved nutritional recovery compared with standard total pancreatectomy.

Factors associated with failure of endoscopic injection haemostasis in bleeding peptic ulcers.

BACKGROUND: The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. METHODS: In the period 1992 to 1998, we prospectively studied all patients suffering from peptic ulcer bleeding and identified endoscopically as being either bleeding actively or carrying a visible vessel. A total of 427 patients (343 men and 84 women; mean age 58.6 +/- 16.6 years) were all subjected to endoscopic injection with adrenaline solution on an emergency basis. Patients who eventually required surgical intervention for permanent haemostasis were considered as endoscopic haemostasis failures, whereas those who did not were considered as endoscopic treatment successes. We evaluated all clinical and endoscopic parameters that might have been related to failure of endoscopic injection therapy. RESULTS: Endoscopic injection haemostasis was successful in 341 patients (79.9%) and a failure in 86 (20.1%) who finally underwent emergency surgical haemostasis. On analysing the examined parameters, failure was significantly related to shock on admission (OR 2.31, 95% CI 1.33, 6.97), spurt bleeding at endoscopy (OR 2.45, 95% CI 1.51, 3.98), posteriorly located duodenal ulcer (OR 2.48, 95% CI 1.37, 7.01) and anastomotic ulcer (OR 3.39, 95% CI 1.37, 7.29). Endoscopic injection haemostasis therapy was less effective in patients with chronic ulcers compared to those who had acute NSAID-related ulcers. A history of peptic ulcer (OR 1.57, 95% CI 1.14, 3.05), previous peptic ulcer bleeding (OR 2.45, 95% CI 1.51, 3.98) or non-use of NSAIDs (OR 2.81, 95% CI 1.33, 4.62) were negative predictors for the outcome of endoscopic haemostasis. CONCLUSION: With the use of specific clinical and endoscopic characteristics it is possible to define a subgroup of high-risk patients for continued bleeding or rebleeding despite endoscopic injection therapy. These patients may be candidates for intensive monitoring, early surgical intervention or possibly complementary endoscopic haemostatic methods.

Gastric ulcers and risk for cancer. Is follow-up necessary for all gastric ulcers?

The aim of this study was to determine the accuracy of initial endoscopy combined with histology and to define whether there is a point in following-up all gastric ulcers until complete healing. We have studied all patients with gastric ulcers documented at endoscopy during a 6-year period. Ulcers were macroscopically characterised as benign or suspicious for malignancy, and biopsies were taken. A follow-up endoscopy and histology was performed 4-6 weeks and 3 months after an anti-ulcer treatment. Resistant ulcers were treated surgically. All patients were followed-up clinically and endoscopically for a year after complete ulcer healing. 802 patients with gastric ulcers were enrolled. At initial endoscopy, 732 ulcers (91.3%) were macroscopically characterised as benign and 70 ulcers (8.7%) as suspicious for malignancy. In the group of endoscopically benign ulcers, only one (0.1%) had malignancy detected by biopsy in the first examination. None of these ulcers turned out to be malignant on subsequent examinations. From the suspicious for malignancy ulcers, 20 (28.6%) were proven to be malignant. Endoscopy may recognise with great accuracy benign ulcers, but it overestimates the malignant ones. The cost-benefit of serial follow-up endoscopies should be re-evaluated in ulcers that appear benign, and biopsies are negative at the initial examination.