Norihiro Haga

Gastrointestinal recovery and outcome after laparoscopy-assisted versus conventional open distal gastrectomy for early gastric cancer

AbstractLaparoscopy-assisted gastrectomy has been increasingly reported as the treatment of choice for early gastric cancer. However, there is little information regarding the benefits of laparoscopy-assisted distal gastrectomy (LADG). LADG and conventional open distal gastrectomy (DG) for early gastric cancer were compared in terms of operative outcome, recovery of bowel function, complications, and changes in body weight. Thirty-four patients underwent LADG for early gastric cancer. These patients were compared with 31 patients who underwent DG during the same period. For estimating gastrointestinal motility recovery, 20 radiopaque markers were inserted into the duodenum during surgery, and abdominal X-rays were taken daily until all markers were seen in the ascending colon. Age, gender, and histologic differentiation of the lesions were matched. The LADG group required a significantly longer operative time and the dissection of fewer lymph nodes. Postoperative hospital stay and the occurrence of postoperative complications (ileus) were significantly shorter and less frequent in the LADG group. The LADG group showed a more rapid recovery of gastrointestinal motor function compared with the DG group during the early postoperative period. Body weight 24 months after LADG was about 100% of pre-illness weight, but no further weight change was encountered in the DG group. For selected patients with early gastric cancer, LADG with lymphadenectomy can provide a rapid recovery and good quality of life without compromising the cure rate.

The technique of laparoscopically assisted total gastrectomy with jejunal interposition for early gastric cancer

BACKGROUND In recent years, laparoscopic gastrectomy has been applied to the treatment of gastric cancer in Japan. However, there are few reports of laparoscopic or laparoscopically assisted total gastrectomy in the treatment of gastric cancer because of the difficulty of the surgical technique. Laparoscopically assisted total gastrectomies with jejunal interpositions were performed on four patients with early gastric cancer located in the upper portion of the stomach. METHODS Four surgical ports were inserted into the abdomen. The stomach was lifted to the abdominal wall using newly developed retraction tubes. Gastric arteries were divided using ultrasonically activated coagulating shears and ligated with ligation forceps. Following these steps, a total gastrectomy reconstruction was performed by jejunal interposition through a small transverse laparotomy. An esophagojejunostomy and a jejunoduodenostomy were made with circular staplers. RESULTS The mean operating time and blood loss were 246 min and 236 ml, respectively. The operations were performed without serious complications. All patients were pain free and ambulatory after the laparoscopically assisted total gastrectomy, and the mean postoperative hospital stay was 16 days. CONCLUSION We successfully performed laparoscopically assisted total gastrectomies in a relatively short period of time. When patients are carefully selected, the laparoscopic procedure can be curative and minimally invasive as a treatment for early gastric cancer.

Gastropyloric motor activity and the effects of erythromycin given orally after esophagectomy

BACKGROUND The motor activity of the gastric tube as an esophageal replacement after esophagectomy is poorly understood. The aims of the present study were to examine the gastropyloric motility of the gastric tube and the effects of erythromycin given orally. METHODS Interdigestive gastropyloric motility was recorded by manometry with a sleeve sensor in 23 esophagectomized patients. The 23 patients were classified into 3-, 12-, and 24-month groups according to postoperative follow-up time. Radiopaque markers were used in 8 patients to assess gastric emptying. The effects of erythromycin were studied after the patients received 600 mg during fasting and 1 g postprandially. RESULTS Compared with the 3-month group, the 12-month group and the 24-month group showed significantly increased pyloric and antral motility, respectively. During a fast, erythromycin induced phase III in 44.4% of the patients with more than 12 months of follow-up. In contrast to the normal subjects, esophagectomized patients showed delayed gastric emptying at 3 and 4 hours. However, erythromycin significantly accelerated gastric emptying at 1, 2, 3, and 4 hours. CONCLUSIONS The motor activity of the gastric tube returns towards normal in a progression over time from the pylorus cephalad. Erythromycin given orally might be used as a prokinetic agent in patients after esophagectomy.

Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog.

BACKGROUND & AIMS Exogenous motilin is believed to stimulate endogenous release of motilin, but this has not been studied in detail. The aim of this study was to investigate whether and by what mechanism exogenous motilin stimulates endogenous release of motilin in the dog. METHODS Gastric and duodenal contractile activity in conscious dogs was monitored by chronically implanted force transducers. Plasma canine motilin (c-motilin) concentrations in response to exogenous porcine motilin (p-motilin) were determined by specific radioimmunoassay for c-motilin. The release of motilin from motilin cells obtained from canine duodenal mucosa was studied in vitro using a perifusion system. RESULTS In vitro, c-motilin release was stimulated by carbachol but not by p-motilin, and the carbachol-induced c-motilin release was inhibited by atropine. In vivo, exogenous p-motilin stimulated endogenous c-motilin release and gastric and duodenal phase III-like contractions; this motilin-induced motilin release was inhibited by atropine, hexamethonium, and a 5-hydroxy-tryptamine 3 receptor antagonist. CONCLUSIONS In the dog, exogenous motilin stimulates endogenous motilin release through muscarinic receptors on motilin-producing cells via preganglionic pathways involving 5-hydroxytryptamine 3 receptors.

Stimulatory mechanism of EM523-induced contractions in postprandial stomach of conscious dogs☆☆☆

BACKGROUND & AIMS EM523, a motilin agonist, is intended to be used as a gastroprokinetic during the postprandial period, but the mechanism(s) by which EM523 stimulates postprandial contractions in the stomach has not been studied before. The aim of this study was to examine the mechanism of contraction-stimulating activity by EM523 in fed dogs. METHODS Contractile activity in the gastric antrum of 5 dogs was monitored using a long-term implanted force transducer and measured by integrating the area under the curve. Test materials were continuously infused or injected intravenously. RESULTS EM523 (1-30 micrograms/kg) induced a dose-dependent increase in fed-type contractions. EM523-induced contractile activity was partially inhibited by atropine, hexamethonium, dopamine, 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and substance P antagonist. Atropine-resistant and EM523-induced contractions were further inhibited by 5-HT3 receptor antagonist and substance P antagonist, and the combined use of the two antagonists completely eliminated the atropine-resistant and EM523-induced contractions. CONCLUSIONS EM523-induced contractions in the fed stomach are quite different from phase III contractions in the fasted state and are mediated partially through the cholinergic pathway. The noncholinergic pathway involves 5-HT3 and neurokinin 1 receptors.

Effect of duodenectomy on gastric motility and gastric hormones in dogs

ObjectiveTo test the hypothesis that the duodenum is required to coordinate interdigestive insulin secretion with gastrointestinal motility and to determine whether duodenectomy alters the interdigestive cycles of plasma motilin and insulin levels and their relations to insulin secretion and motility. MethodsAdult mongrel dogs were chronically implanted with force transducers in the stomach, duodenum, and upper jejunum to monitor contractile activity. Eight healthy mongrel dogs were divided into control and duodenectomized dogs. Insulin secretion, gastrointestinal motility, and plasma concentrations of motilin during the interdigestive period were measured in normal and duodenectomized dogs. ResultsAfter duodenectomy, no obvious phase III contractions were seen in the gastric antrum, but migrating phase III contractions were seen in the upper jejunum. The plasma motilin concentration did not fluctuate as it does in normal dogs, and remained low. After duodenectomy, insulin secretory cycles were not coordinated with either cycles of interdigestive motility or the plasma concentration of motilin. Exogenous motilin administration stimulated endogenous insulin release significantly compared with saline-treated controls. The contractile response of the stomach to exogenous motilin after duodenectomy was similar to that of intact dogs. ConclusionsDuodenectomy disrupts the relation between cycles of both interdigestive gastrointestinal motility and insulin secretion. These effects of duodenectomy may be attributable to interruption of the duodenopancreatic neural connections, hormonal abnormalities, or loss of vagus-sensitive humoral factors. The duodenum, which stores motilin, seems to play an important role in the relations between gastric migrating motor complexes and the concomitant increase of insulin secretion in fasted dogs. The mechanism responsible for the effect of motilin in both duodenectomized and normal dogs may involve a cholinergic pathway.

Motilin controls cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs

The effect of motilin on insulin release has not been studied in the interdigestive state. Adult mongrel dogs were chronically implanted with force transducers in the stomach and duodenum to monitor contractile activity, and the plasma motilin and insulin concentrations were measured by a specific radioimmunoassay and enzyme immunoassay, respectively. The concentration of insulin in plasma was found to fluctuate in close association with that of motilin and phase III of the interdigestive migrating contractions in the stomach. This spontaneous release of insulin was mimicked by intravenous infusion of motilin at a dose of 0.3 μg ⋅ kg-1 ⋅ h-1. Exogenous motilin (0.01-0.3 μg/kg) dose dependently stimulated insulin release, which was abolished by atropine, hexamethonium, ondansetron, and truncal vagotomy. Phentolamine significantly enhanced, whereas propranolol inhibited, motilin-induced insulin release. In a perifusion system using islet cells from the canine pancreas, motilin did not affect insulin release. In conclusion, motilin stimulates insulin release through vagal cholinergic, muscarinic receptors on pancreatic β-cells, and the effect appears to be modulated by adrenergic nerves.The effect of motilin on insulin release has not been studied in the interdigestive state. Adult mongrel dogs were chronically implanted with force transducers in the stomach and duodenum to monitor contractile activity, and the plasma motilin and insulin concentrations were measured by a specific radioimmunoassay and enzyme immunoassay, respectively. The concentration of insulin in plasma was found to fluctuate in close association with that of motilin and phase III of the interdigestive migrating contractions in the stomach. This spontaneous release of insulin was mimicked by intravenous infusion of motilin at a dose of 0.3 microgram.kg-1.h-1. Exogenous motilin (0.01-0.3 microgram/kg) dose dependently stimulated insulin release, which was abolished by atropine, hexamethonium, ondansetron, and truncal vagotomy. Phentolamine significantly enhanced, whereas propranolol inhibited, motilin-induced insulin release. In a perifusion system using islet cells from the canine pancreas, motilin did not affect insulin release. In conclusion, motilin stimulates insulin release through vagal cholinergic, muscarinic receptors on pancreatic beta-cells, and the effect appears to be modulated by adrenergic nerves.

Pyloric motility after pylorus-preserving gastrectomy with or without the pyloric branch of the vagus nerve.

An attempt was made to examine gastropyloric motility after pylorus-preserving gastrectomy (PPG) and to determine the influence of the pyloric branch of the vagus nerve in the dog. Fifteen dogs were divided into three groups of five. PPG with preservation (PPPG) and resection of the pyloric branch of the vagus (RPPG) were performed, and controls were prepared. Interdigestive and digestive gastropyloroduodenal motility was recorded after a 2-week recovery period using strain-gauge force transducers (SG). Radiopaque markers (ROMs) were used to assess gastric emptying. No significant differences were found between PPPG and RPPG in terms of gastropyloroduodenal motility during either the interdigestive or the postprandial state. During phase III of the interdigestive state, pyloric relaxation correlated with contraction of the gastric body after both PPPG and RPPG. During the first month it was accompanied by tonic and phasic pyloric contractions after feeding and delayed gastric emptying in two groups. By the end of the first month these pyloric contractions had diminished, and the rate of gastric emptying was similar to that of the controls. We concluded that it is not necessary to preserve the pyloric branch of the vagus for gastropyloroduodenal motility after PPG. Gastric stasis during the early postoperative period is due to tonic and phasic contractions of the pylorus.RésuméOn a examiné la motilité gastropylorique après gastrectomie avec conservation du pylore (GCP) et notamment, le rôle de la branche pylorique du nerf vague chez le chien. Quinze chiens ont été divisés en trois groupes de cinq, un groupe de contrôle, un deuxième groupe de GCP et un troisième avec résection de la branche pylorique du nerf vague (RBPV). On a enregistré la motilité gastropyloroduodénale interdigestive et digestive après une période de deux semaines à l’aide de transducteurs «strain gauge force» (SGF). Des marqueurs radio-opaques ont été utilisés pour évaluer la vidange gastrique. On n’a observé aucune différence statistiquement significative entre les groupes GCP et RBPV en ce qui concerne la motilité gastropyloroduodénale pendant la période interdigestive ou postprandiale. Pendant la phase III de l’état interdigestif, la relaxation pylorique était couplée à une contraction du corps gastrique après la GCP et la RBPV. Pendant le premier mois, elle était accompagnée de contractions pyloriques toniques et phasiques après l’alimentation et un retard de la vidange gastrique dans les deux groupes. Cependant, après un mois, ces contractions avaient diminué et la prévalence de vidange retardée était similaire aux contrôles. En conclusion, il ne semble pas nécessaire de conserver la branche pylorique du vague pour la motilité gastropyloroduodénale après GCP. La stase gastrique postopératoire précoce est en rapport avec des contractions toniques et phasiques du pylore.ResumenSe realiza un estudio experimental en perros para dilucidar la acción de la rama pilórica del n. Vago en la motilidad gastro-pilórica, tras una gastrectomía con preservación del píloro (PPG). Se utilizaron 15 perros divididos en 3 grupos de cinco. El grupo control, el grupo PPG, con preservación de la rama pilórica del vago (PPPG), y el grupo con resección de dicho nervio (RPPG). Se registró, transcurridas dos semanas de la operación, la motilidad gastropilórica-duodenal interdigestiva y digestiva, utilizando un transductor que mide la fuerza de necesaria para modificar el calibre (SG). Para evaluar el vaciamiento gástrico se emplearon marcadores radiopacos (ROMs). No se registró diferencia alguna entre los grupos PPPG y RPPG, por lo que se refiere a la motilidad gastropilórica-duodenal tanto interdigestiva como postprandial. En la fase III del estadio interdigestivo, la relajación del píloro se asociaba a una contracción del cuerpo gástrico tanto en el grupo PPPG como en el RPPG. Durante el primer mes (tras la operación) se constataron tras la ingesta, tanto en un grupo como en el otro, contracciones tónicas y fásicas del píloro, con retraso en el vaciamiento gástrico. Sin embargo, al finalizar el primer mes, las contracciones pilóricas disminuyeron y el vaciamiento gástrico fue similar al observado en el grupo control. Conclusión: Por lo que a la motilidad gastropilórica-duodenal tras PPG se refiere, no se precisa conservar la rama pilórica del n. Vago. La estasis gástrica durante el periodo postoperatorio precoz se debe a las contracciones tónicas y fásicas del píloro.

Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors in the vagal pathway and gallbladder in the dog

The mechanism of CCK action on gallbladder contractions in the physiological condition is unclear. Gallbladder contractions were monitored by means of chronically implanted force transducers in conscious dogs. Postprandial gallbladder contractions were partially inhibited by atropine and hexamethonium, and completely inhibited by devazepide. In vitro contractile response of canine gallbladder muscle strips to CCK-8 was also studied. CCK-8-induced muscle strip contraction was atropine and tetrodotoxin resistant, but was completely eliminated by devazepide. The existence of CCK receptors in the vagal nerve and gallbladder was examined by means of autoradiography. Forty-eight hours after ligation of the abdominal vagus, CCK-8 binding sites were found to accumulate in the subdiaphragmatic vagal nerve immediately proximal to the ligature, and similar binding sites were also found in the gallbladder smooth muscle layer. These binding sites were displaced by the addition of 10(-7) mol/1 unlabeled CCK-8 and devazepide, but L-365,260 had no effect. In conclusion, it is considerable that postprandial CCK-induced gallbladder contractions are controlled through CCK-A receptors both on the vagal nerve in stimulating endogenous release of acetylcholine and on the gallbladder directly to stimulate muscle contraction in the dog.

Pyloric relaxation regulated via intramural neural pathway of the antrum

Current information about pyloric relaxation is not sufficient. For this reason, our study aimed at measuring pyloric relaxation correctly and determining the role of the intrinsic and extrinsic neural pathway in pyloric relaxation. Five groups of dogs were used: five dogs had an intact gastrointestinal tract (control group); five dogs had transection and reanastomosis of the antrum 3 cm proximal to the pylorus (antral transection group); five dogs had extrinsic pyloric denervation (denervation group); five dogs had transection and reanastomosis of the antrum with extrinsic pyloric ring denervation (transection with denervation group); and five dogs had truncal vagotomy (vagotomy group). Gastropyloroduodenal motility was recorded by a strain-gauge force transducer in conscious dogs. In the control and denervation groups, pyloric relaxation was observed only during phase III of the interdigestive migrating motor complex. In the antral transection, transection with denervation, and vagotomy groups, pyloric relaxation was not observed in either the interdigestive or the postprandial state. The frequency of pyloric contractions increased in these groups in comparison with the control group. In conclusion, the results suggest that pyloric relaxation occurred during phase III to expel undigested particles from the stomach and that descending antral intramural pathways play an important role in the control of pyloric relaxation.