Esophageal perforation in South of Sweden: Results of surgical treatment in 125 consecutive patients

<p>Abstract</p> <p>Background</p> <p>For many years there has been a debate as to which is the method of choice in treating patients with esophageal perforation. The literature consists mainly of small case series. Strategies for aiding patients struck with this disease is changing as new and less traumatic treatment options are developing. We studied a relatively large consecutive material of esophageal perforations in an effort to evaluate prognostic factors, diagnostic efforts and treatment strategy in these patients.</p> <p>Methods</p> <p>125 consecutive patients treated at the University Hospital of Lund from 1970 to 2006 were studied retrospectively. Prognostic factors were evaluated using the Cox proportional hazards model.</p> <p>Results</p> <p>Pre-operative ASA score was the only factor that significantly influenced outcome. Neck incision for cervical perforation (n = 8) and treatment with a covered stent with or without open drainage for a thoracic perforation (n = 6) had the lowest mortality. Esophageal resection (n = 8) had the highest mortality. A CAT scan or an oesophageal X-ray with oral contrast were the most efficient diagnostic tools. The preferred treatment strategy changed over the course of the study period, from a more aggressive surgical approach towards using covered stents to seal the perforation.</p> <p>Conclusion</p> <p>Pre-operative ASA score was the only factor that significantly influenced outcome in this study. Treatment strategies are changing as less traumatic options have become available. Sealing an esophageal perforation with a covered stent, in combination with open or closed drainage when necessary, is a promising treatment strategy.</p

Role of corticotropin-releasing factor, somatostatin and leptin in vagal nerve function and control of gastric emptying

The overall aim of this thesis was to study the effects of centrally acting CRF and leptin, and peripherally acting somatostatin on gastric emptying of glucose. Freely moving rats bearing chronic intragastric fistulas received intragastric infusions (1.0 ml/min) of glucose (12.5 % or 25 %) during 6-18 min. The stomachs were evacuated immediately, or 6-36 min after intragastric infusion offset, and solute emptied was determined. Drugs were delivered into the lateral (i.c.v.) or fourth (4th i.c.v.) cerebral ventricle, or injected subcutaneously. In some experiments, animals were sacrificed by decapitation. and trunk blood was collected for subsequent RIA analysis of gastrointestinal hormones. Presence of leptin receptor-like immunoreactivity in nuclei of the caudal brainstem, and the possible co-localization with choline-acetyl transferase, was studied with immunohistochemistry. CRF injected i.c.v. (60 pmol-1.28 nmol) increased plasma levels of somatostatin in freely fed rats, but did not affect plasma levels of CCK or gastrin. Plasma levels of somatostatin were unaffected by CRF in food deprived rats, as well as in food deprived rats pretreated with 10 µg CCK, i.p. Peripheral (i.p.) injection did not affect plasma levels of somatostatin, CCK or gastrin. To evaluate the effect of peripheral somatostatin receptor activation on gastric emptying, rats received injections of the agonist octreotide (0.0013-1.39 µg/kg, s.c.). OctreodOctreotidede dose dependently suppressed gastric emptying during gastric fill. The effect was reversed by pretreatment with CPP-1, but not by subdiaphragmatic vagotomy. A new finding was that the octreotide-induced emptying suppression during fill was followed by a rapid increase in postprandial emptying, and the transition was locked to the offset of the intragastric infusion, regardless of its duration. Administration of CRF (10-1000 pmol) 4th i.c.v., suppressed gastric emptying of glucose during gastric fill, indicating that CRF acts in the caudal brainstem to suppress emptying. The CRF-induced emptying suppression was blocked by pretreatment with the somatostatin antagonist CPP-1 (40 µg/kg. s.c.), which by itself was without effect, suggesting that the brainstern CRF-elicited suppression of gastric emptying was mediated by peripheral somatostatin. The data suggest a novel, CRF-somatostatin linkage mechanism in the brainstem control of gastric emptying. Immunohistochemistry using an antibody that recognizes all leptin receptor (LR) isoforms equally, showed many strongly immunoreactive (IR) neurones in the dorsal motor nucleus of the vagus nerve (DMX) of rats. There were only weakly LR-IR neurones present in the nucleus of the solitary tract (NTS) and in the hypoglossal nucleus. In the DMX, LR-IR was co-localized with choline-acetyltransferase. The data suggest that LR are present in cholinergic neurones of the DMX Injection of leptin (0.013-3.9 µg) 4th i.c.v. suppressed gastric emptying of glucose during fill, but did not affect postprandial emptying. The suppression of emptying during fill was abolished by vagotomy, but not by pretreatment with a CRF antagonist. The data show that leptin acts in the caudal brainstem, independently of CRF receptor activation, to suppress gastric emptying through a vagal route. The findings are consistent with the notion of functionally significant leptin receptors in the DMX of rats. Subdiaphragmatic vagotomy, as well as gastric branch vagotomy, increased gastric emptying of glucose during gastric fill. Gastric branch vagotomy was without effect on postprandial emptying, whereas subdiaphragmatic: vagotomy slightly decreased emptying in the post-fill period. These findings show that the gastric branch of the vagus contributes to inhibition of emptying during gastric fill, whereas other vagal fibers appear to contribute to control of emptying after fill. In addition, the findings support the notion of separable control mechanisms for glucose gastric emptying during versus after gastric fill

Peptides that regulate food intake - Separable mechanisms for dorsal hindbrain CART peptide to inhibit gastric emptying and food intake

We investigated whether dorsal hindbrain and/or peripheral cocaine- and amphetamine-regulated transcript peptide (CARTp) acts to suppress gastric emptying of a caloric stimulus. Furthermore, effects of dorsal hindbrain CARTp on sucrose consumption and licking microstructure was studied, as well as the possible contribution of corticotropin-releasing factor (CRF) receptors to mediate effects of CARTp downstream on emptying and sucrose intake. Rats bearing gastric fistulas received intragastric infusions (1.0 ml/min) of 12 ml 12.5% glucose. Gastric samples were withdrawn immediately after the intragastric infusion to reflect emptying during gastric fill. CARTp injected in the fourth ventricle intracerebroventricularly (0.5 and 1.0 mug) suppressed gastric emptying. CARTp reduced sucrose intake at similar doses and altered a variety of lick microstructure variables ( no. of licks, bursts, clusters, licks/burst, licks/clusters, interlick interval, first meal size, and first meal duration). Pretreatment with the CRF antagonist alpha-helical CRF-(9- 41) blocked the effect of 1.0 mug CARTp on gastric emptying but not on sucrose consumed or on any of the licking microstructure parameters. These data demonstrate differential mediation of the feeding and gastric inhibitory effects of CARTp and suggest that CARTp-induced inhibition of gastric emptying does not contribute to this peptide's ability to inhibit food intake

Total gastrectomy causes a sustained, long-term elevation of somatostatin in plasma, independent of the mode of reconstruction in pigs.

AIM: The long-term effects of gastrectomy and various reconstructions of the gastrointestinal tract on fasting plasma levels of gastrointestinal hormones known to contribute to the control of gastrointestinal motor function were evaluated in pigs. MATERIALS AND METHODS: Domestic pigs were randomly selected to sham surgery or total gastrectomy (TG) followed by reconstruction with oesophago-jejunostomy on a Roux-en-Y loop (OJRY), jejunal interposition between the oesophagus and the duodenum (OJD), or an oesophagojejunostomy with a proximal jejunal pouch reservoir (J-pouch) on a Roux-en-Y loop. Blood was collected just before surgery and ten weeks later and peptide levels were analysed by radioimmunoassay. RESULTS: Somatostatin levels were sustained at a high level after TG, regardless of the mode of reconstruction, but were significantly lower in sham-operated animals. Levels of vasoactive intestinal peptide (VIP), neurotensin and motilin were unchanged. CONCLUSION: TG by itself leads to high levels of somatostatin long term, however, somatostatin, motilin, neurotensin and VIP are unaffected by the mode of reconstruction

Validation of the paracetamol absorption test for measuring gastric tube emptying in esophagectomized patients versus gold standard scintigraphy.

Scintigraphy is the gold standard for objective measurement of delayed gastric tube emptying after esophagectomy. The aim of this pilot study is to validate, by reference to scintigraphy, the paracetamol absorption test for measuring gastric tube emptying in esophagectomized patients

Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine- and amphetamine-regulated transcript Peptide-induced hypophagia in rats.

Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress nutritional intake after administration into the fourth intracerebral ventricle. Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase-activating polypeptide (PACAP) fragment, could act as a competitive antagonist against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we show for the first time in vivo that the reduction in solid food intake induced by exogenous CARTp 55-102 (0.3 nmol: 1.5 µg) administered fourth i.c.v. is blocked by pretreatment with PACAP 6-38 (3 nmol). The PACAP 6-38 fragment had no effect by itself either when given into the fourth ventricle or subcutaneously. Although effective to block the CARTp-effect on feeding and short-term body weight, PACAP 6-38 failed to attenuate CARTp-associated gross motor behavioral changes suggesting at least two CARTp-sensitive receptor subtypes. In conclusion, PACAP 6-38 acts as a functional CARTp antagonist in vivo and blocks its effects on feeding and short term weight gain

Jejunal pouch reconstruction but not preservation of duodenal passage after total gastrectomy reduces plasma cholecystokinin and pancreatic polypeptide long term in pigs.

AIM: The long-term effects of reconstructions of the gastrointestinal tract after gastrectomy on plasma levels of gastrointestinal hormones that contribute to food intake controls were evaluated. MATERIALS AND METHODS: Domestic pigs were randomly assigned to sham-surgery or total gastrectomy followed by reconstruction with oesophagojejunostomy on a Roux-en-Y loop (OJRY), jejunal interposition between the oesophagus and the duodenum (OJD), or an oesophagojejunostomy with a jejunal pouch reservoir (J-pouch) on a Roux-en-Y loop. Plasma levels of peptides were analysed by radioimmunoassay (RIA). RESULTS: Ten weeks after surgery, levels of cholecystokinin (CCK) and pancreatic polypeptide (PP) were significantly lowered (79.6% and 67.0%, respectively) in animals with a J-pouch, but not in sham-operated animals or animals with OJRY or OJD, as compared to preoperative levels. The levels of neuropeptide Y (NPY) and peptide YY (PYY) remained unchanged, irrespective of the mode of reconstruction. CONCLUSION: J-pouch, but not preservation of duodenal passage after total gastrectomy, lowers levels of CCK and PP, peptides that reduce food intake

Pretreatment with a CRF antagonist amplifies feeding inhibition induced by fourth ventricular cocaine- and amphetamine-regulated transcript peptide

Abstract Background Pre-treatment with the corticotropin-releasing factor antagonist α-helical CRF9-41 prevents inhibition of gastric emptying by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level, but its inhibition of sucrose intake is not affected. This is suggestive of separable underlying mechanisms of action in the caudal brainstem for cocaine-and amphetamine-regulated transcript peptide with regard to food intake and gastrointestinal functions. Here we further examine cocaine-and amphetamine-regulated transcript peptide—corticotropin-releasing factor receptor interactions in caudal brainstem controls of solid food intake. Injections of combinations of vehicle, cocaine-and amphetamine-regulated transcript peptide (0.5 μg or 1 μg) or α-helical CRF9-41 were given into the fourth cerebral ventricle of rats. Nocturnal solid food intake was recorded over 22 h. Results Pre-treatment with α-helical CRF9-41 into the fourth ventricle significantly increased the responsivity to cocaine-and amphetamine-regulated transcript peptide on hypophagia. In a separate control experiment, α-helical CRF9-41 pre-treatment blocked CRF-induced food intake inhibition indicative of its antagonistic effectiveness. Conclusions We conclude that an endogenous Corticotropin-releasing factor agonist may modulate suppression of food intake caused by cocaine-and amphetamine-regulated transcript peptide at a dorsal hindbrain level in the absence of stress. A potential caudal brainstem mechanism whereby cocaine-and amphetamine-regulated transcript peptide effects on food intake is attenuated via corticotropin-releasing factor receptor activity causing tonic inhibition, is suggested