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Effects of in vivo heregulin beta1 treatment in wild-type and ErbB gene-targeted mice depend on receptor levels and pregnancy.

Mice heterozygous (+/-) for either heregulin (HRG), ErbB2, or ErbB3 were created by gene targeting, resulting in the loss of one functional gene copy and an associated decrease in targeted protein. We examined the in vivo activity of recombinant HRG peptide, rHRG beta1 (amino acids 177 to 241), in the three heterozygous mouse lines and in wild-type (WT) mice, both pregnant and nonpregnant. Nonpregnant WT and HRG(+/-) mice of both sexes were sensitive to rHRG beta1 treatment as evidenced by a high mortality rate associated with abdominal enlargement and parietal cell loss. However, pregnant WT mice and ErbB2 and ErbB3 heterozygous mice treated with rHRG beta1 were less affected, with significantly lower mortality rates and a less severe abdominal phenotype. Histological analysis revealed extensive breast ductal hyperplasia in females of all genotypes after rHRG beta1 treatment. Hyperplasia of other epithelial tissues such as the pancreas and intestine and the growth of cardiac nerve bundles were also observed, independent of sex.

Animals↗

Gastrointestinal angiodysplasia in congenital platelet dysfunction.

We herein report three cases of repeated massive bleeding from the stomach and small bowel. One patient suffered from both thrombasthenia (type II) and von Willebrand disease (type 1) simultaneously. Two others had Bernard-Soulier's syndrome (BSS). One patient with BSS had bleeding from gastric angiodysplasia and was treated endoscopically by clipping. The other patients had massive bleeding from the small intestine, and had partial resection of the affected small intestine. Histologically, irregular dilatation and proliferation of the blood vessels were demonstrated in the submucosa in bleeding spots from a resected small intestine, and these findings were consistent with the features of acquired angiodysplasia. The development of gastrointestinal angiodysplasia may not only be associated with a dysfunction of von Willebrand factor but also with that of platelets.

Adult↗

Localized hyperplastic gastropathy of the mucous cell- and mixed cell-type (localized Ménétrier's disease): a report of 11 patients.

Clinical and pathologic findings in five women and six men with the rare localized form of hyperplastic gastropathy of the mucous cell-(foveolar) or mixed cell-(mucous cell and glandular) type are reported. Upper abdominal discomfort, loss of appetite, loss of weight, and anemia were the principal symptoms. Preoperative hypoproteinemia was documented in two patients. Gross findings consisted of a circumscribed area of giant folds, well demarcated from the surrounding normal-appearing mucosa, located predominantly in the corpus in six patients and predominantly in the antrum in four patients. Histologically they corresponded to an increase in the epithelial cell mass principally of mucous cells with elongated and sometimes cystically dilated foveolae, accompanied by a mild inflammatory infiltrate. This so-called localized form of hyperplastic gastropathy has been known since the first description of the disease but has gained relatively little attention in the literature. However, its recognition seems diagnostically important and pathogenetically interesting. Etiology, pathogenesis, and the natural history are mostly unknown. Five of the 11 patients had concomitant adenocarcinoma of the stomach. In four of them the carcinoma was not located within but outside the area of hyperplasia. Because of that and because of a rather unusual accumulation of other tumors of the gastrointestinal tract in these patients, it is suggested that localized hyperplastic gastropathy could be an indicator of an increased risk for gastrointestinal tumors in general more than a possibly premalignant lesion by itself.

Adenocarcinoma↗

Monitoring of gastric acidity following ductal decompression surgery for chronic pancreatitis.

The accepted decompression methods of chronic pancreatitis are the longitudinal pancreaticogastrostomy and the conventional pancreaticojejunostomy. The aim of the present study was to estimate the effect of these types of drainage operations on gastric acidity and to evaluate the clinical results. Between Jan. 1992 to 1996 56 patients with chronic pancreatitis were selected into the investigation who were operated in our clinic. A 24 hour gastric monitoring was taken on every patient before and 6 weeks after the operation. Following a complete postoperative check up we found that both types of operations are effective for pain relief (71%). Retrospectively 83% of the patients had no digestive problems due to pancreatic enzyme substitution. According to our statistical evaluation of 24 hour gastric pH monitoring test no alteration was detected in gastric pH in both groups pre- and postoperatively. On the basis of pH measuring and evaluated data we consider that pancreaticogastrostomy is a good operation choice to relieve intractable pain in selected patients with chronic pancreatitis associated with duct dilatation.

Chronic Disease↗

Transhiatal esophagectomy for treatment of benign and malignant esophageal disease.

Since our initial 1978 report, we have performed transhiatal esophagectomy (THE) in 1085 patients with intrathoracic esophageal disease: 285 (26%) benign lesions and 800 (74%) malignant lesions (4.5% upper, 22% middle, and 73.5% lower third/cardia). THE was possible in 97% of patients in whom it was attempted; reconstruction was performed at the same operation in all but six patients. The esophageal substitute was positioned in the original esophageal bed in 98%, stomach being used in 782 patients (96%) and colon in those with a prior gastric resection. Hospital mortality was 4%, with three deaths due to uncontrollable intraoperative hemorrhage. Major complications included anastomotic leak (13%), atelectasis/pneumonia prolonging hospitalization (2%), recurrent laryngeal nerve paralysis, chylothorax, and tracheal laceration (< 1% each). There were five reoperations for mediastinal bleeding within 24 hours of THE. Intraoperative blood loss averaged 689 ml. Altogether, 78% of the patients had no postoperative complications. Actuarial survival of the cancer patients mirrors that reported after transthoracic esophagectomy. Late functional results are good or excellent in 80%. Approximately 50% have required one or more anastomotic dilatations. With intensive preadmission pulmonary and physical conditioning, use of a side-to-side staple technique (which has reduced the cervical esophagogastric anastomotic leak rate to less than 3%), and postoperative epidural anesthesia, the need for an intensive care unit stay has been eliminated and the length of hospital stay was reduced to 7 days. We concluded that THE can be achieved in most patients requiring esophageal resection for benign and malignant disease and with greater safety and less morbidity than the traditional transthoracic approaches.

Anastomosis, Surgical↗

[Residual gastric mucosa after gastrectomy: development of precancerous lesions].

The gastric remnant can be regarded as a model to investigate the events of gastric carcinogenesis of intestinal type. Histologic changes precursor of the malignancy develop in higher incidence in the postoperative stomachs than in non-resected ones. 316 patients hemi-gastrectomized for peptic ulcer were assessed by an endoscopic-histologic study to provide further informations on the sequential chain of histologic lesions that precede the development of cancer. The anastomosis was by far the commonest diseased area at endoscopy, particularly in the patients with a Billroth II resection (p < 0.0004). The 10% of the 233 patients biopsied evidenced a normal gastric mucosa, in the others Superficial Gastritis 74%, Chronic Atrophic Gastritis 36%, Cystic Dilatation 52%, Foveolar Hyperplasia 29%, Intestinal Metaplasia 39%, moderate-severe Dysplasia 6% as single abnormality or variously associated were observed. The stoma was the most damaged area at histology. The occurrence of the DC, the FI and the IM at the anastomotic site was significative (p values between 0.02 and 0.001). The earliest postoperative histologic lesion was the CAG, evidenced, in mean 13 years after operation, the latest the DC observed in mean 18 years after surgery (p < 0.004). The IM, the IF, the CD, and the dysplasia in association with the CAG were observed at postoperative intervals shorter when non-associated with CAG (respective p value: NS, < 0.03, < 0.0002, NS). The probability of transition from an histologic lesions to a more advanced one in our patients was similar to that of a non resected population at medium--high risk of gastric cancer.

Female↗

Initial results with a stapled gastrojejunostomy for the laparoscopic isolated roux-en-Y gastric bypass.

BACKGROUND: The gastric pouch to jejunum anastomosis is a critical step in the performance of an isolated Roux-en-Y gastric bypass. When performing this procedure laparoscopically, intracorporeal suturing of the gastric pouch to Roux-en-Y jejunum anastomosis is technically demanding, time consuming, and perhaps the most prohibitive part of the operation. We devised a unique, effective, and simple method to perform this anastomosis using an EEA stapler. This report describes this technique and its follow-up in our series of patients undergoing a laparoscopic isolated Roux-en-Y gastric bypass utilizing this technique. METHODS: A prospective analysis was performed identifying the technical success, leak rate, and postoperative incidence of anastomotic stenosis and its management in a consecutive series of patients undergoing a laparoscopic isolated Roux-en-Y gastric bypass with a gastrojejunal anastomosis constructed with a 21-mm or 25-mm EEA stapler. RESULTS: Forty-eight patients underwent laparoscopic isolated Roux-en-Y gastric bypass. Mean age was 40.9 years (range 22 to 64) and mean body mass index was 52.3 kg/m(2) (range 31 to 76 kg/m(2)). There were no mortalities. Three patients (6.3%) were converted to an open procedure, but only 1 because of an inability to perform the gastrojejunal anastomosis (short jejunal mesentery). There was 1 leak (2.1%) from the gastrojejunal anastomosis. It was successfully managed nonoperatively. Thirteen patients (27.1%) patients developed an anastomotic stenosis requiring endoscopic balloon dilatation. Seven of the 13 patients required only a single dilatation and have had no recurrence of dysphagia. Six of the 13 patients needed 2 to 4 dilatations, and all are swallowing normally. None have required surgical revision. After 12 months of follow-up, the mean weight loss was 115 pounds and mean decrease in body mass index was 18.5 kg/m(2). CONCLUSIONS: The stapled EEA gastrojejunal anastomosis for the laparoscopic isolated Roux-en-Y gastric bypass is safe and effective. Anastomotic stenosis occurs in approximately one quarter of patients, but it can be managed well with endoscopic balloon dilatation.

Adult↗

Delineation of the gastric muscularis mucosae and assessment of depth of invasion of early gastric cancer using a 20-megahertz endoscopic ultrasound probe.

Using a 20 MHz endoscopic ultrasound system, delineation of the gastric muscularis mucosae and estimation of the depth of malignant invasion was attempted by in vivo scanning during the process of routine endoscopic observation or in vitro scanning of excised sections of 34 early gastric cancers in 32 patients. The muscularis mucosae was visualized as a single hypoechoic layer in 16 of 32 lesions (50%) scanned in vitro. Comparison of lesions in which delineation of the muscularis mucosae was or was not possible revealed no significant differences with respect to either the thickness of the lamina propria and muscularis mucosae or with respect to the degree of inflammatory cell infiltration of the lamina propria or the conditions of the boundary between the lamina propria and the muscularis mucosae. This indicates that improvement of the operability characteristics of the ultrasonic apparatus will be needed to achieve improved delineation of the muscularis mucosae. The accuracy of invasion depth estimation of early gastric cancer was 67% (16 of 24 lesions scanned in vivo) and 73% (8 of 11 lesions) in cases in vivo where the muscularis mucosae and the tumor were delineated on the same screen. The principal factors causing erroneous staging were the presence of dilated benign glandular ducts, ulcer scars, and attenuation of the ultrasound waves.

Aged↗

Retrosternal pedicled jejunum interposition: an alternative for reconstruction after total esophago-gastrectomy.

OBJECTIVE: If the colon cannot be used for reconstruction after total esophago-gastrectomy, alternatives have to be sought. METHODS: From 1990 to 2001, retrosternal jejunum loop interposition was performed in 35 patients (male/female: 29:6; mean age 59.2, range 16-83 years) due to cancer in 32 cases and to esophageal perforation in three cases. In all patients reconstruction with stomach or colon, respectively, was impossible on behalf of the underlying histology, of previous resection of the stomach and impedient colonic diseases. A jejunal segment with abundant arcades was chosen, preserving a strong, distal arteriovenous mesenteric pedicle, while 2-3 proximal mesenteric vessels were severed. The loop was pulled up retrosternally, establishing a cervical end-to-side esophagojejunostomy. A Roux-en-Y anastomosis was done in a convenient position. RESULTS: Two patients died perioperatively due to mediastinitis and consecutive multiorgan failure (one Boerhaave's syndrome, one suicidal ingestion of acid). In one case the oral part of the loop developed venous congestion and was replaced by a free jejunal transplant. The perioperative course of 32 patients was uneventful. Seventeen patients are up and well (1-8.5 years). Sixteen patients died of metastatic disease. The functional results are satisfactory. In about 50% of patients recurrent dilatations became necessary due to anastomotic scars. However, none of the patients complained about severe dysphagia. CONCLUSION: In cases of impedient colonic diseases, the pedicled, retrosternal jejunal loop with cervical anastomosis is an alternative for reconstruction after total esophagogastrectomy.

Adolescent↗

An unusual case of massive gastric distension with catastrophic sequelae.

We report a case of massive gastric distension presenting with abdominal pain, shock and lower limb ischaemia. At laparotomy, gastric distension was found to be secondary to gastric outflow obstruction compounded by gas formation from antacid ingestion. Both the aorta and inferior vena cava were directly compressed by the distended stomach. This mode of presentation and combined aetiologies remain unreported. Gastric decompression resulted in profound cardiovascular compromise, multiorgan failure and eventually death.

Abdominal Pain↗

Gastric arteriolar and venular responses to nitrogenous and nonnitrogenous vasodilating agents in the rat.

We made in vivo microvascular observations to simultaneously compare the actions of various direct vasodilators on the resistance and capacitance vessels without confounding systemic hemodynamic effects. The responses of gastric submucosal arteriolar and venular diameters to the topical application of 10(-7) 10(-5), and 10(-3) M of the vasodilators nitroglycerin (NTG), sodium nitroprusside (SNP), hydralazine (HYD), and adenosine (ADN), and acetylcholine (ACh) were studied in 6 rats for each agent using in vivo microscopy. The basal diameters of arterioles, 37 +/- 2 microns (mean +/- SE), were maximally dilated to 86 +/- 2 microns by 10(-3) M ADN, NTG, SNP or ACh, while with 10(-3) M HYD dilation was just 55%. The basal diameters of venules, 36 +/- 2 microns, were maximally dilated only to 51 +/- 1 micron by 10(-3) M ADN, NTG or SNP, while those by 10(-3) M HYD and ACh were 60 and 71%, respectively. We observed that: (1) NTG and SNP were the strongest arteriolar and venular dilators, but at low dose (10(-7) M), NTG was more effective than SNP. (2) Gastric submucosal venules had considerably less dilating capacity than arterioles. (3) ADN was as effective as NTG and SNP for both arteriolar and venular dilation at 10(-3) M. It was less potent at lower concentrations. (4) ACh was as potent as ADN, NTG and SNP in dilating arterioles, but it was notably less potent in dilating venules. (5) HYD was the weakest arteriolar and venular dilator among all agents studied, and its action on venules was slightly greater than that on arterioles.

Animals↗

Esophagogastric anastomosis performed with a stapler: the occurrence of leakage and stricture.

The circular stapler has lowered the leakage rate of an esophageal anastomosis to a level hitherto achieved by only a few surgeons performing hand anastomosis on selected patients with carcinoma of the esophagus. However, the esophageal anastomosis performed with a stapler is also associated with a high stricture rate. Our prospective study was conducted to determine the leakage rate and the incidence of stricture after esophagogastric anastomosis was performed with a stapler, the relationship of stricture to the size of the stapler, and the risk of stricture in relation to time. In a group of 174 patients with carcinoma of the thoracic esophagus, resection was performed, and a one-stage esophagogastric anastomosis was constructed. There were 33 hand anastomoses, 64 anastomoses with an EEA stapler (U.S. Surgical Corp., Norwalk, Conn.), and 77 anastomoses with an ILS stapler (Ethicon Ltd., Edinburgh, U.K.). The anastomotic leakage rate was 3.4% (6/174); 3% with the hand technique and 3.5% with the stapler technique (4.7% for the EEA and 2.6% for the ILS). After leakages and hospital deaths were excluded, 133 discharged patients were evaluated for the occurrence of anastomotic strictures. Only those who complained of dysphagia were investigated. The incidence of stricture for hand anastomosis was 8.7%-EEA 20% and ILS 10%; the overall incidence of anastomoses with a stapler was 14.5%. The true incidence would probably be higher if all patients were assessed by endoscopic or radiologic examination after operation. All three sizes of EEA staplers had a high incidence of stricture. For the ILS stapler the 25 mm size had the highest stricture rate (28.6%) of all groups, but for the 29 and 33 mm sizes, the incidences were 5.3% and 0%, respectively. Actuarial analysis showed an increasing risk of stricture with a reduction in the size of stapler used and was 32.5% and 35%, respectively, for the ILS 25 mm and EEA 25 mm staplers at 131/2 months. The risk of stricture occurrence was highest in the first 4 months. Treatment by bougienage was satisfactory. In conclusion, esophagogastric anastomosis performed with a stapler is a very safe procedure with respect to leakage but is associated with a high risk of stricture, except when the largest ILS staplers are used. However, dilatation readily overcomes the stricture occurrence and adequately compensates for the reduced leakage rate and its attendant serious consequences.

Esophageal Neoplasms↗

Laparoscopic Heller myotomy with bolstering partial posterior fundoplication for achalasia.

BACKGROUND: The ideal antireflux procedure following laparoscopic Heller myotomy for achalasia is controversial. We present a novel laparoscopic technique of partial posterior fundoplication to bolster the myotomy. METHODS: Between August 1998 and March 2002, eight patients (five females and three males; median age, 40 years) underwent a laparoscopic Heller myotomy with bolstering partial posterior fundoplication. Results of barium swallow and manometry studies were consistent with achalasia. Failed medical treatments included balloon dilation, botulinum injection, and calcium channel blockers. RESULTS: The preoperative weight loss was 33 lb (range, 10-50) with a mean duration of symptoms of 29 months (range, 12-72). Seventy-one percent of the patients had reflux. Myotomy was confirmed with endoscopic guidance. Partial posterior fundoplication was performed with the edges of the myotomy on the right and left sides sutured to the stomach, which covered the myotomy. No conversion was required. In one patient, a perforation was recognized, repaired, and bolstered. The mean operative blood loss was 72 mL (range, 30-150). The mean operative time was 4 hours. Patients resumed solids at 2.5 days (range, 2-5). Postoperative complications included subcutaneous emphysema (n = 1), pneumothorax (n = 1), and umbilical port hernia (n = 1). None of the patients had reflux symptoms at 3 to 18 months of follow-up. CONCLUSION: Laparoscopic Heller myotomy with partial posterior fundoplication is technically feasible and effectively prevents reflux symptoms. Bolstering the myotomy may help heal small esophageal perforations.

Adult↗

[Diaphragmatic contraction in the lower esophageal sphincter pressure in Chagas disease patients].

Contraction of the crural diaphragm increases the lower esophageal sphincter (LES) pressure, which is important for preventing gastroesophageal reflux. Our objective in this study was to compare the influence of diaphragmatic contraction on LES pressure of Chagas' disease patients with dysphagia, and control volunteers. We studied 17 patients with positive serologic reactions for Chagas' disease, dysphagia and slow transit of barium sulphate through the esophagus. Two also had esophageal dilatation. Twelve healthy volunteers were the control group. LES pressure was measured by the station pull-through (SPT) method with a round manometric catheter with four side holes opened at the same level, 10 cm from the end of the catheter, infused with water at a flow of 0.5 ml/minute. The catheter was introduced through the nose until the four side holes reached the stomach. After five minutes of stabilization it was withdrawn 1 cm every 15 seconds while the patient or volunteer breathed normally. We measured the difference in LES pressure recorded at inspiration and expiration, which is the contribution of the diaphragmatic contraction to LES pressure. There was no difference in this value between controls (18.5 +/- 9.6 mmHg, mean +/- SD) and patients (17.9 +/- 7.6 mmHg, P > 0.05). The value increased with LES pressure, suggesting that the diaphragm may participate in LES pressure asymmetry. We conclude that the diaphragmatic contribution to LES pressure in Chagas' disease patients is the same as that of normal subjects.

Adult↗

Minimally invasive surgery: hepatobiliary-pancreatic and foregut.

This review is confined to the liver, biliary tract, pancreas, and foregut (oesophagus and stomach). The issues relating to laparoscopic cholecystectomy mainly concern the bile duct injuries associated with this operation. This review provides some evidence that although the risk for this iatrogenic injury is declining, it continues to be a problem and is accompanied by significant morbidity, mortality, and a huge escalation in care costs. Laparoscopic clearance of ductal stones is undoubtedly safe and effective, and issues have now focused on comparisons between this form of management and orthodox endoscopic clearance. Laparoscopic cardiomyotomy may well replace other forms of treatment of achalasia, including balloon dilation and botulinum toxin injection. As the results of laparoscopic antireflux surgery have been so good in the medium term, the question of medical versus laparoscopic treatment is being addressed by two randomized clinical trials. Gastric resection is established only in respect of excision of mesenchymal tumours. Gastric surgery for advanced gastric cancer must still be regarded as developmental. Laparoscopic liver resections and in situ ablation are still confined to developing centres, but the early results are promising. However, simpler hepatic procedures, such as de-roofing of symptomatic simple hepatic cysts, are well established and in widespread practice. Only a few centres have published their results on laparoscopic pancreatic surgery. The early reported outcome for internal drainage of pancreatic pseudocysts, enucleation of benign insulinomas, and distal pancreatic resections has been good, but the experience is limited.

Bile Duct Neoplasms↗

Helicobacter pylori vacuolating toxin accumulates within the endosomal-vacuolar compartment of cultured gastric cells and potentiates the vacuolating activity of ammonia.

This study explored the relationship between vacuolating toxin and ammonia in the genesis of Helicobacter pylori-induced vacuolation in cultured human gastric cells and investigated the intracellular sites of toxin accumulation. Neutral red dye uptake and electron microscopy were used in the investigation of the respective roles of, and of the reciprocal interaction between, toxin and ammonia in cell vacuolation and ultrastructural immunocytochemistry was used for the identification of the intracellular sites of internalized toxin. Toxin was found to cause an expansion of the endosomal compartment, where it accumulates after cellular internalization. However, toxin does not form large, neutral red-positive vacuoles unless combined with ammonia, whose moderate vacuolating activity is markedly potentiated by the toxin. It is concluded that the toxin accumulated within the endosomal compartment alters the morphology and function of this organelle and plays a permissive role towards cell vacuolation, possibly by increasing the accumulation of protonated ammonia within endosomes. In turn, ammonia induces excessive dilatation of the endosomes with reciprocal fusion of their membranes, thus causing cytoplasmic vacuolation.

Ammonia↗

Incidence and management of benign anastomotic stricture after cervical oesophagogastrostomy.

Benign anastomotic stricture after transhiatal oesophagectomy and gastric tube reconstruction constitutes a major problem. From August 1988 to April 1991, 81 patients were followed after cervical oesophagogastrostomy. Twenty-four patients (30 per cent) developed a benign anastomotic stricture 3-23 (median 8) weeks after operation. Poor vascularization of the gastric tube, determined during operation, and postoperative anastomotic leakage were statistically significant risk factors for stricture formation. Symptoms related to stricture were often typical and were confirmed by endoscopy and/or radiography. Radiography did not yield information additional to that obtained from endoscopy. Strictures were treated in the outpatient clinic by dilatation with Savary dilators. Repeated dilatation completely alleviated dysphagia in 20 of the 24 patients (83 per cent). In ten patients dilatations could be discontinued after a median of 8 (range 1-17) sessions. Dilatation was continued until the end of follow-up in nine patients or until death from recurrent disease in five. No complications of dilatation were seen.

Adult↗

Peritoneal mesothelioma: hypertrophic gastroepiploic and omental arteries identified by radioimmune angiography.

We report a first case of malignant peritoneal mesothelioma examined by radioimmune (RI) angiography with technetium-99m human serum albumin. The RI angiography clearly demonstrated the characteristic findings including hypertrophic gastroepiploic arteries and dilated omental branches. These findings may be very helpful in distinguishing malignant peritoneal mesotheliomas from peritoneal carcinomatosis.

Adult↗