Sequential evaluation of gastric intraluminal prostaglandin E2 release, acid secretion and DNA-flow cytometry in N-methyl-N-nitro-N-nitrosoguanidine gastric carcinogenesis in the rat.

The study was initiated to evaluate the sequential changes of gastric intraluminal prostaglandin E2 (PGE2), gastric acid secretion and of the DNA-flowcytometric patterns during gastric carcinogenesis induced by 45-week N-methyl-N-nitro-N-nitrosoguanidine (NG) administration in the rat. Twenty male chronic gastric fistula Sprague-Dawley rats received NG solution (120 mg/l) for 45 weeks and 20 were used as controls. Samples of gastric juice (1 h) were obtained from all animals under basal conditions and every 5 weeks until the end of the experiment. Aliquots of gastric juice were titrated with 0.1 N NaOH. Other aliquots were extracted with ethylacetate and processed for specific PGE2 RIA. On the day following gastric juice collection a gastric lavage and gastric biopsies (n = 4) were obtained through the fistula and processed for flowcytometry. All surviving animals were killed after 45 weeks and histology was obtained. The incidence of cancer in NG treated chronic gastric fistula rats was 66%. Flowcytometry segregated at an early stage (30-35 weeks) those animals which were to develop gastric carcinoma from those which were not. Administration of NG decreased gastric secretion volume, acid and intraluminal PGE2 concentration both in animals developing and not developing cancer. During the last 10 weeks a sharp rise in gastric intraluminal PGE2 concentration was observed in tumor-bearing animals only probably due to production by tumor cells. Prostaglandin deficiency may contribute to the NG-induced mucosal damage and may be involved in gastric carcinogenesis.

Time-related interference of misoprostol with experimental gastric cancer formation induced by N-methyl-N'-nitro-N-nitrosoguanidine in the rat.

The purpose of this study was to investigate the effect of long-term misoprostol administration, at non-antisecretory doses, on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-induced gastric carcinogenesis. The incidence of gastric carcinomas and precancerous lesions was evaluated in 50 male 250-g Sprague-Dawley rats after 52 weeks of continuous oral administration of MNNG (120 mg/l; n = 20), MNNG plus misoprostol (2 mg kg-1 day-1; n = 20) or tap water (n = 10) (experiment 1), and in 30 rats treated with MNNG for 30 weeks followed by tap water (n = 15) or by misoprostol (n = 15) for 22 weeks; a third group (n = 10) received tap water only for 52 weeks (experiment 2). After sacrifice, gastric mucosal lesions were macroscopically evaluated and their histology obtained. MNNG consumption was comparable in all groups (6.5 +/- 1.1 mg rat-1 day-1). Misoprostol consumption was 180 +/- 0.25 mg kg-1 day-1 rat-1. In experiment 1 the incidence of gastric carcinomas was 60% in the MNNG group and 25% in the group treated with MNNG plus misoprostol (P less than 0.05). Cytotoxic and hyperplastic gastric mucosal lesions were also significantly reduced by misoprostol. In experiment 2 the incidence of carcinomas was 31% and 38.6% respectively. Misoprostol significantly decreased the incidence of gastric cancer formation when given from the beginning of the experiment. By contrast, when administered after 30 weeks of MNNG treatment it did not interfere with experimental gastric cancer formation. Exogenous prostaglandins are able to prevent the early MNNG-induced gastric mucosal lesions, thus interfering with gastric carcinogenesis.

Role of prostaglandins in the early phases of experimental gastric carcinogenesis in the rat.

The study was initiated to evaluate the effect of N-methyl-N-nitro-N-nitrosoguanidine (NG) on gastric intraluminal prostaglandin release during a 30-day treatment period and to investigate the effect of a stable prostaglandin E1 analogue (misoprostol) on NG-induced gastric mucosal damage during the same time period. Samples of gastric juice (1 h) were obtained from 40 male Sprague-Dawley rats with chronic gastric fistulas, in basal conditions and after 5, 15 and 30 days of continuous oral administration of NG (120 mg/l) or tap water. Aliquots of gastric juice were titrated with 0.1 M NaOH. Other aliquots were extracted with ethyl acetate and subjected to specific radioimmunoassay for prostaglandin E2. The severity of gastric mucosal lesions was evaluated in 60 rats after 5 days and 30 days of continuous oral administration of NG (120 mg/l) or NG plus misoprostol (200 micrograms/kg-1/day-1) or tap water, and a histological study was carried out. Administration of NG induced a significant decrease of gastric intraluminal prostaglandin E2 concentration at 15 and 30 days. Oral administration of misoprostol, at non-antisecretory doses, protected the rats against NG-induced gastric mucosal damage. Prostaglandins may be involved in the early phases of experimental gastric carcinogenesis.

Prostaglandin generation in the gastric mucosa of rats with stress ulcer.

Prostaglandins, normally synthesized by the gastric mucosa, have been shown to prevent the formation of experimentally induced ulcers, including stress ulcers. A physiologic role of these compounds in the protection of the gastric mucosa has been postulated. In order to assess the role of endogenous prostaglandins in the pathogenesis of stress ulceration, we measured the amounts of prostaglandin E (PGE) generated by gastric mucosal samples from rats exposed to cold restraint stress. Stress induced a significant inhibition of PGE biosynthesis by the gastric mucosa. The inhibition was similar to that caused by indomethacin. The degree of inhibition of PGE generation significantly correlated with the severity of the gastric mucosal lesions (P less than 0.001). Identical effects were identified in antrum and fundus. The decrease of PGE mucosal biosynthesis seems to be a major determinant in the pathogenesis of stress ulceration.

Prostaglandins in commercial milk preparations. Their effect in the prevention of stress-induced gastric ulcer.

To determine if prostaglandins might be the gastroduodenal mucosal protective components in milk, concentrations of prostaglandin E2 (PGE2), thromboxane B2, and 6-keto-PGF1 alpha (the major metabolite of prostacyclin) were measured in aliquots of commercial milk. Whole milk, heavy cream, and yogurt each contained more than 3 ng/mL of PGE2, whereas low-fat milk (2.04 +/- 0.18 ng/mL) and milk from three nursing mothers (0.66 +/- 0.05 ng/mL) contained substantially less. Levels of thromboxane and prostacyclin were much lower, in general, less than 500 pg/mL. In a cold-restraint stress ulcer model in rats, milk was able to inhibit the development of gastric ulcers (50% and ulcer index 5.0 +/- 2.1 v control, 90% and 18.9 +/- 3.8, respectively). Charcoal treatment, which depleted more than 95% of the prostaglandins, rendered the milk nonprotective (80% and ulcer index 15.0 +/- 1.4). These observations are consistent with the concept that prostaglandins may be responsible for the presumed beneficial effects of milk in the prevention and treatment of peptic ulcer disease.

Effect of ceruletide on pituitary-hypothalamic peptides and on emotion in man.

In order to clarify the mechanism of the analgesic effect of ceruletide (CRL), the peptides B-endorphin (BE), ACTH, prolactin (PRL), growth hormone (GH) and substance P were determined in the basal state and following IV CRL administration in 11 patients. CRL, at the dose of 2 ng/kg/min, significantly augmented BE levels in the plasma, and in CSF. Substance P levels were significantly augmented by CRL in the plasma, while ACTH levels were significantly augmented in CSF. GH and PRL levels were not affected by CRL. Placebo had no effect on any of the measured peptides. The effect of CRL on mood and anxiety, known to be affected by opioids, was studied in 14 patients with psychogenic headache. The effect of histamine induced headache on State trait anxiety inventory and on Mood adjective check list was studied before and after administration of placebo or CRL. CRL significantly diminished anxiety when compared to placebo. Elation, surgency and egotism were significantly augmented while skepticism was significantly diminished by CRL. The CRL effect on mood and pain may be mediated by augmented levels of neurohormones both in the plasma and in CSF.

The effect of somatostatin and 16,16-dimethyl-prostaglandin E2 on bombesin-stimulated canine gastric acid, plasma gastrin and pancreatic polypeptide secretion.

We studied the effect of the intravenous infusion of 16,16-dimethylprostaglandin E2 methyl ester (di-M-PGE2) and somatostatin on bombesin-stimulated gastric acid secretion, plasma gastrin and plasma pancreatic polypeptide in four chronic gastric fistula dogs. Bombesin-stimulated gastric acid secretion was significantly inhibited by somatostatin and virtually abolished by di-M-PGE2. Both agents caused significant, but indistinguishable inhibition of gastrin release (P less than 0.05). Bombesin-stimulated pancreatic polypeptide release was also significantly inhibited by both somatostatin and di-M-PGE2; the inhibitory effect of somatostatin was significantly greater than that of di-M-PGE2 (P less than 0.05). This study provides further evidence in support of the complex interrelationships between agents responsible for the modulation of gastrointestinal physiology.

111In-pentetreotide detection of gastrinoma before and after surgery.

Eighteen patients with Zollinger-Ellison syndrome were studied with 111In-pentetreotide SPECT in order to localize gastrinoma, the tumour responsible for this pathology. NMR imaging was also carried out. Eight patients were operated. 111In-pentetreotide was reinjected 4 hours before operation and the radioactivity of the excised tumours counted. The nature of the withdrawn tissues was assessed by immunohistochemistry (chromogranina A). The scintigraphy was repeated 3-6 months after surgery. 111In pentetreotide SPECT was more sensitive than NMR. It was also absolutely specific because all the radioactive tumours excised showed positive chromogranin A staining. The radioactivity/gram counted in gastrinomas exceeded 10 fold the hepatic and biliary radioactivity and 20-100 folds the radioactivity of blood and omentum. In all the operated patients but three, the scintigraphy performed after surgery did not detect tumours. However complete eradication did not occur, because though 3-6 months after surgery the gastrinemia was significantly lower with respect to pre-surgery results it did not return to normal values in all patients but two.

Cimetidine and antacid prophylaxis of acute upper gastrointestinal bleeding in high risk patients. Controlled, randomized trial.

A randomized, controlled clinical trial was performed to compare the efficacy of prophylactic cimetidine treatment, antacid treatment and no treatment in high risk patients. Sixty patients received cimetidine (200 mg every 6 hours), 52 patients received antacids (Maalox, 10 ml/hour), and 56 patients received no treatment. One hundred thirty-five patients completed the study. Eight patients in the control group and one patient in the antacid-treated group presented with upper gastrointestinal bleeding. No bleeding occurred in the cimetidine-treated group. Patients considered at low risk had no bleeding. Cimetidine or antacid prophylaxis significantly decreased the incidence of upper gastrointestinal bleeding in the high risk patients.

Retained antral mucosa in pancreaticoduodenectomy patients.

Thirteen patients with pancreaticoduodenectomy were studied. In three patients presenting with stomal ulcer or bleeding stomitis, endoscopic biopsies showed the presence of retained antral mucosa (RAM). No disease and no RAM was present in the remaining ten patients. Bombesin (BBS) infusion augmented both gastric acid and gastrin secretion in the group with RAM, whereas no change was apparent in the remaining ten patients. The BBS infusion test is useful in detecting stomal ulcer high risk pancreaticoduodenectomy patients.

Management and long-term results in patients with two-thirds gastrectomy and stomal ulcer.

In 67 patients with two-thirds gastrectomy and endoscopically proven stomal ulcer, serum gastrin levels were measured under basal conditions and after intravenous infusion of bombesin (15 ng/kg/min), calcium (4 mg/kg/hour) and secretion (2 units/kg). All patients underwent medical or surgical therapy. The long-term results were evaluated according to the Visick grading system (average follow-up, 3.1 years).

Laparoscopic resection of solitary gastric schwannoma.

We report a case of successful laparoscopic resection of a solitary schwannoma of the gastric fundus performed on emergency. The patient was a 52-year-old man who presented with an upper gastrointestinal hemorrhage. At admission, the endoscopy and hydro-CT scan showed a submucosal tumor, 2.5 cm in maximum diameter, with an area of central ulceration arising from the anterior wall of the gastric fundus. A wedge laparoscopic resection of the gastric wall was performed under endoscopic guidance. The defect in the anterior wall was repaired in part by linear stapler and in part using a continuous suture. The postoperative recovery was uneventful and the patient was discharged on the 4th postoperative day. Laparoscopic approach represents a safe and efficient approach for the treatment of benign tumors of the stomach, also on emergency basis.

[Echographic and ERCP-manometric study of gallbladder and Oddi's sphincter behavior in biliary colic in patients with cholelithiasis. Effects of cerulein]. / Studio ecografico e CPRE-manometrico del comportamento della colecisti e dello sfintere di Oddi in corso di colica biliare in pazienti con colelitiasi. Effetto della ceruleina.

In a previous study, we have shown that caerulein relieves biliary colic pain in gallstone patients. This study was initiated to determine gallbladder and sphincter of Oddi behaviour during biliary colic and their response to caerulein. In 10 gallstone patients gallbladder volume was measured by real-time ultrasonography during a biliary colic episode and 72 hours after cessation of pain, before and after caerulein administration. Basal sphincter of Oddi pressure was determined by CPRE manometry in 10 gallstone patients during biliary colic and three days after cessation of pain, before and after caerulein. The results of this study show that, during biliary colic, gallbladder volume is 8 times greater than in the post-colic state. Basal sphincter of Oddi pressure was also significantly higher during biliary colic than in the post-colic state. Caerulein relieved in all cases the biliary colic pain while reducing gallbladder volume and decreasing the sphincter of Oddi.

[Laparoscopic inguinal hernia repair "IPOM" with Dual-Mesh]. / Ernioplastica inguinale laparoscopica "IPOM" con Dual-Mesh.

The authors report their experience on laparoscopic hernioplasty using the Intraperitoneal Onlay Mesh Repair (IPOM) in 56 patients. 34 patients had a bilateral hernia, 6 of which were recurrent and 22 had a monolateral hernia, of which 9 had recurrent hernia. Overall, a total of 90 hernias were treated. The hernia repair was performed utilizing "GORE-TEX DualMesh Plus biomaterial with holes" in the first 32 cases and the latest "...Corduroy" type in the remaining 24 cases. The prostheses were fixed with titanium spiral tacks (Protack, AutoSuture, Tyco Healthcare). No intraoperative complications occurred and no conversion was necessary. Five minor post-operative complications (5.5%), 2 seromas and 3 transient paresthesias, were observed. Four patients (7.1%) needed analgesics after the first 24 hours. Mean hospital stay was 36 hours, with a minimum of 24 and a maximum of 48. Mean resumption of normal activity was 8 days with return to work within two weeks. At an average 18 months follow-up, 3 recurrences were recorded (3.3%). The results of this study as well as the meta-analysis of the series presented in the Literature, indicate that the IPOM may be a feasible, safe and effective procedure in the treatment of recurrent and bilateral hernias or when a hernia repair is performed during other laparoscopic procedures. The IPOM has infact been shown to be faster and easier than the other more commonly performed laparoscopic hernioplasties (TAPP and TEP). These data may also suggest to utilize this technique in particular cases of primitive hernia such as very active young males or heavy duty workers. However the limited series and the short follow-up ask for randomized prospective long term studies to definitely ascertain the true incidence of recurrence and therefore the effectiveness of this attractive procedure.

Effect of nizatidine versus ranitidine on gastric intraluminal prostaglandin release in duodenal ulcer patients.

The role of prostaglandins in peptic ulcer disease and their relation to Helicobacter pylori infection remain controversial. This study sought to compare the effects of oral nizatidine and ranitidine on the gastric mucosal release of prostanoids in duodenal ulcer (DU) patients and to correlate prostanoid concentrations with H. pylori status. Twenty-eight patients with DUs were randomized to receive either nizatidine or ranitidine. Nizatidine 300 mg at night elevated intraluminal PGE2 concentrations; 6-keto-PGF1 alpha concentrations also rose, but did not reach statistical significance. Ranitidine induced non-significant falls in PGE2 and 6-keto-PGE1 alpha concentrations. Patients with H. pylori infection had lower PGE2 and 6-keto-PGF1 alpha concentrations than non-infected patients, but nizatidine was equally effective in increasing prostanoid levels in both groups. These findings may be considered as favourable side effects of nizatidine with uncertain clinical significance. Further studies are needed to elucidate the synergism between prostanoids, eradication of H. pylori and nizatidine in the treatment of DU.

[Laparoscopic cholecystectomy: analysis of first 203 cases]. / Colecistectomia per via laparoscopica: analisi dei primi 203 casi.

Laparoscopic cholecystectomy is a valid alternative to open cholecystectomy. The Authors present their experience in the management of 208 consecutive patients. The low incidence of complications, the short hospital stay as well as earlier return to work, and lower medical expenses are the advantages of laparoscopic surgery. The latter is, therefore, more suitable for the treatment of benign gallbladder diseases.

BioEnterics Intragastric Balloon (BIB): a short-term, double-blind, randomised, controlled, crossover study on weight reduction in morbidly obese patients.

BACKGROUND: The BioEnterics Intragastric Balloon (BIB) System in association with restricted diet has been used for the short-term treatment of morbid obesity. Aim of this study was to evaluate the real, short term, efficacy of the BIB for weight reduction in morbidly obese patients by using a prospective, double-blind, randomised, sham-controlled, crossover study. METHODS: Patients were recruited from January 2003 to December 2003. After selection, they were randomly allocated into two groups: BIB followed by sham procedure after 3 months (Group A), and sham procedure followed by BIB after 3 months (Group B). All endoscopic procedures were performed under unconscious intravenous sedation. The BioEnterics Intragastric Balloon (Inamed Health; Santa Barbara, CA, USA) was filled by using saline (500 ml) and methylene blue (10 ml). Patients were discharged with omeprazole therapy and diet (1000 kcal). Patients were followed up weekly by a physician blinded to randomisation. In both groups mortality, complications, BMI, BMI reduction and %EWL were considered. Data were expressed as mean +/- s.d., except as otherwise indicated. Statistical analysis was performed by means of Student's t-test, Fisher's exact test or chi (2) with Yates correction; P < 0.05 was considered significant. RESULTS: A total of 32 patients were selected and entered the study (8M/24F; mean age: 36.2 +/- 5.6 years, range 25-50 years; mean BMI 43.7+/-1.5 kg/m(2), range 40-45 kg/m(2); mean %EW: 43.1 +/- 13.1, range: 35-65). All patients completed the study. Mortality was absent. Complications related to endoscopy, balloon placement and removal were absent. Mean time of BIB positioning was 15 +/- 2 min, range 10-20 min. After the first 3 months of the study, in Group A patients the mean BMI significantly (P < 0.001) lowered from 43.5 +/- 1.1 to 38.0 +/- 2.6 kg/m(2), while in Group B patients the decrease was not significant (from 43.6 +/- 1.8 to 43.1 +/- 2.8 kg/m(2)). The mean %EWL was significantly higher in Group A than in Group B (34.0 +/- 4.8 vs 2.1 +/- 1%; P < 0.001). After crossover, at the end of the following 3 months, the BMI lowered from 38.0 +/- 2.6 to 37.1 +/- 3.4 kg/m(2) and from 43.1 +/- 2.8 to 38.8 +/- 3.1 kg/m(2) in Groups A and B, respectively. CONCLUSIONS: The results of this study show that treatment of obese patients with BioEnterics Intragastric Balloon is a safe and effective procedure. In association with appropriate diet it is significantly effective in weight reduction when compared to sham procedure plus diet. The BIB procedure can play a role in weight reduction in morbidly obese patients or in the preoperative treatment of bariatric patients.

Role of thyrotropin-releasing hormone in stress ulcer formation in the rat.

The role of the hypothalamic peptide thyrotropin-releasing hormone in stress ulcer formation was investigated. In experiment 1, TRH was peripherally administered (10 micrograms/kg) to rats subjected to cold-restraint stress and compared to an inactive peptide; in experiment 2, TRH was administered intracerebroventricularly (0.02, 0.1, and 0.5 microgram/kg) to rats with no adjunctive experimental stress; in experiment 3, TRH antiserum was given intracerebroventricularly to rats subjected to stress and compared to normal rabbit serum. When TRH was administered subcutaneously in rats subjected to stress, it significantly aggravated ulcer formation, and this effect was inhibited by atropine and vagotomy. When administered intracerebroventricularly, TRH alone induced, in a dose-dependent fashion, the formation of gastric ulcers. TRH antiserum infused intracerebroventricularly inhibited ulcer formation induced by cold-restraint stress. In conclusion, TRH seems to play a role in stress ulcer formation, possibly by a cholinergic mediated mechanism.