Yoshitaka Toyomasu

Laparoscopically assisted total gastrectomy with lymph node dissection for upper and middle gastric cancer

BackgroundIn recent years, laparoscopic gastrectomy has been applied for the treatment of gastric cancer in Japan and Western countries. This report describes the short- and long-term results for patients with gastric cancer who underwent laparoscopically assisted total gastrectomy (LATG) with lymph node dissection.MethodsFrom September 1999 to December 2007, 20 patients underwent LATG, and 18 underwent conventional open total gastrectomy (OTG) for upper and middle gastric cancer. The indications for LATG included depth of tumor invasion limited to the mucosa or submucosa and absence of lymph node metastases in preoperative examinations. The LATG and OTG procedures for gastric cancer were compared in terms of pathologic findings, operative outcome, complications, and survival.ResultsNo significant difference was found between LATG and OTG in terms of operation time (254 vs 248xa0min.), number of lymph nodes (26 vs 35), complication rate (25% vs 17%), or 5-year cumulative survival rate (95% vs 90.9%). Differences between LATG and OTG were found with regard to blood loss (299 vs 758xa0g) and postoperative hospitalization (19 vs 29xa0days).ConclusionFor properly selected patients, laparoscopically assisted total gastrectomy can be a curative and minimally invasive treatment for early gastric cancer.

Intragastric administration of rikkunshito stimulates upper gastrointestinal motility and gastric emptying in conscious dogs

BackgroundTraditional Japanese medicine, known as Kampo medicine, consists of mixtures of several medicinal herbs widely used to treat upper gastrointestinal disorders in Japan. Rikkunshito, one of these medicines, has not been evaluated with respect to its influence on gastrointestinal motor activity. We investigated the effect of rikkunshito on upper gastrointestinal motility and plasma ghrelin concentrations in conscious dogs.MethodsContractile response to intragastric administration of rikkunshito was studied via surgically implanted force transducers. A powdered extract of rikkunshito (1.3, 2.7, and 4.0xa0g) dissolved in water was administered into the stomachs of normal and vagotomized dogs before feeding and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and ondansetron) were injected intravenously before intragastric administration of rikkunshito. Plasma acylated ghrelin levels after intragastric administration of rikkunshito were measured.ResultsIn a fasting state, intragastric administration of rikkunshito induced phasic contractions in the duodenum and jejunum in normal dogs. Rikkunshito-induced contractions were inhibited by atropine, hexamethonium and ondansetron. In vagotomized dogs, rikkunshito induced phasic contractions, similar to normal dogs. Gastric emptying was accelerated by intragastric administration of rikkunshito in a dose-dependent manner. The plasma acylated ghrelin level 150xa0min after intragastric administration of 4.0xa0g of rikkunshito was significantly higher than the control value.ConclusionsIntragastric administration of rikkunshito stimulates gastrointestinal contractions in the interdigestive state through cholinergic neurons and 5-HT type 3 receptors. Moreover, rikkunshito increases plasma acylated ghrelin levels. Rikkunshito may alleviate gastrointestinal disorders through its prokinetic effects.

Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans

Background The aim of this study was to investigate the effects of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans. Methods The study was performed as a crossover design, and ten unresectable or relapsed gastric cancer patients were randomly divided into two groups. Group A (n = 5) was started on Rikkunshito (2.5 g three times daily, orally) from the first course of chemotherapy and followed by a second course without Rikkunshito. A treatment with reversed order was performed for Group B (n = 5). All patients received combined chemotherapy with S-1 plus cisplatin. The primary endpoint was the amount of oral intake, and the categories of scales of anorexia, nausea, and vomiting; secondary endpoints included the plasma concentration of acylated ghrelin. Results In the Rikkunshito-on period, no decrease of the plasma concentration of acylated ghrelin induced by cisplatin was observed. The average oral intake in the Rikkunshito-on period was significantly larger than that in the Rikkunshito-off period, and the grade of anorexia was significantly lower in the Rikkunshito-on period than in the Rikkunshito-off period. Conclusion Rikkunshito appeared to prevent anorexia induced by cisplatin, resulting in effective prophylactic administration of chemotherapy with cisplatin, and patients could continue their treatments on schedule.

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.

Intragastric monosodium l-glutamate stimulates motility of upper gut via vagus nerve in conscious dogs

Monosodium l-glutamate (MSG) is a substance known to produce the umami taste. Recent studies indicate that MSG also stimulates a variety of activities in the gastrointestinal tract through its receptor in the gut, but no study has reported the activity in conscious large experimental animals. The aim of our study was to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Contractile response to intraluminal injection of MSG was studied in the fed and fasted states by means of chronically implanted force transducers. MSG (5, 15, 45, and 90 mM/kg) dissolved in water was injected into the stomach and duodenum in normal and vagotomized dogs. MSG solution was administered into the stomach before feeding, and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and granisetron) were injected intravenously before MSG administration to the stomach. The effect of MSG was investigated in Pavlov (vagally innervated corpus pouch), Heidenhain (vagally denervated corpus pouch), and antral pouch (vagally innervated) dogs. Upper gut motility was significantly increased by intragastric MSG but not significantly stimulated by intraduodenal MSG. Intragastric MSG (45 mM/kg) stimulated postprandial motility and accelerated gastric emptying. MSG-induced contractions were inhibited by truncal vagotomy, atropine, hexamethonium, and granisetron. Gut motility was increased by intrapouch injection of MSG in the Pavlov pouch, but it was not affected in the Heidenhain or antral pouch dogs. We conclude that intragastric MSG stimulates upper gut motility and accelerates gastric emptying. The sensory structure of MSG is present in the gastric corpus, and the signal is mediated by the vagus nerve.

Clinical Significance of Melanoma Antigen-Encoding Gene-1 (MAGE-1) Expression and its Correlation with Poor Prognosis in Differentiated Advanced Gastric Cancer

BackgroundMelanoma antigen-encoding gene-1 (MAGE-1), a cancer/testis antigen, has been reported to be expressed in various types of cancer. We investigated the clinicopathological features and prognostic significance of MAGE-1 expression in advanced gastric cancer (AGC).MethodsImmunohistochemical staining for MAGE-1 was performed on surgical specimens obtained from 135 patients with AGC.ResultsPositive expression of MAGE-1 detected in cytoplasm was observed in 44 of 135 cases (32.6%) in primary tumors and 26 of 96 (27.1%) in lymph node metastases. In noncancerous gastric tissues, apparent MAGE-1 expression was not detected. MAGE-1 in primary tumor was correlated with advanced age (Pxa0<xa00.001), macroscopic infiltrated type (Pxa0=xa00.035), and presence of vascular invasion (Pxa0=xa00.027). The 5-year cancer-specific survival rates of AGC patients with positive MAGE-1 expression were significantly lower than those of patients with negative MAGE-1 (positive: 31.6%, negative: 57.6%, Pxa0=xa00.038). On multivariate analysis, MAGE-1 expression was not an independent prognostic predictor of AGC (Pxa0=xa00.064). In differentiated AGC patients, MAGE-1 expression was correlated with advanced age (Pxa0=xa00.003), macroscopic infiltrated type (Pxa0=xa00.009), and presence of lymph node metastasis (Pxa0=xa00.033). The cancer-specific survival rates of differentiated AGC patients with positive MAGE-1 were significantly lower than those of patients with negative MAGE-1 (Pxa0=xa00.003). Positive MAGE-1 expression was an independent prognostic factor of differentiated AGC patients on multivariate analysis (Pxa0=xa00.031).ConclusionsThese findings suggest that MAGE-1 protein expression can serve as a predictive marker of poor prognosis in differentiated AGC patients.

Laparoscopy-assisted proximal gastrectomy with gastric tube reconstruction for early gastric cancer

BackgroundIn this report, laparoscopy-assisted proximal gastrectomy (LAPG) and gastric tube reconstruction using a mini-loop retractor (MLR) is described for the treatment of early gastric cancer.MethodsEarly upper gastric carcinoma with no metastasis had been diagnosed in the subjects of this study. Five surgical ports were inserted into the abdomen. The stomach was lifted to the abdominal wall side with a MLR. Three of five gastric arteries were divided using ultrasonically activated coagulating shears and ligated with ligation forceps. A fixed gastric part with MLR was properly changed according to the lymph node dissection. Reconstruction with a gastric tube (20xa0cm long, 3xa0cm wide) using a circular stapler was performed through a small incision, through which the specimen was removed.ResultsFourteen patients underwent LAPG. The mean operating time and blood loss were 202xa0min and 236xa0ml, respectively. The operations were performed without serious complications. None was changed to a laparotomy, and there were no deaths.ConclusionsThis technique of LAPG and gastric tube reconstruction using MLR for the treatment of proximal early gastric cancer was simple and safe.

Mosapride Citrate Improves Postoperative Ileus of Patients with Colectomy

Background and AimsPostoperative ileus is a transient bowel dysmotility that occurs following many types of operations and is a common complication of gastrointestinal surgery. Mosapride citrate is an agonist of the 5-hydroxytryptamine 4 receptor and accelerates upper gut motility. No study has evaluated its effect on gastrointestinal motility after surgery. The aim of this study was to investigate whether mosapride citrate reduces the duration of postoperative ileus.MethodsThirty patients with colon cancer who underwent colectomy were divided into two groups: the mosapride group and the control group. The mosapride group received mosapride 15xa0mg by mouth with a minimal amount of water three times a day, starting on postoperative dayxa01. The control group received only a minimal amount of water on the same schedule. Patients were allowed to resume oral feeding on postoperative dayxa04. Postoperative time to first flatus and defecation were evaluated, and the amount of food intake was observed. Gastrointestinal motility was recorded on postoperative dayxa08.ResultsThe appearance ratio of interdigestive migrating contractions and the motility index at the antrum and duodenum were significantly higher in the mosapride group than in the control group. The time to first flatus and defecation were significantly shorter in the mosapride group than in the control group. The amount of food intake on postoperative daysxa06 and 7 was significantly larger in the mosapride group than in the control group.ConclusionMosapride citrate reduces the duration of postoperative ileus and may improve outcomes after gastrointestinal surgery.

Nesfatin-1 Suppresses Gastric Contractions and Inhibits Interdigestive Migrating Contractions in Conscious Dogs

AbstractBackgroundNesfatin-1 is a novel 82-amino acid anorectic peptide. Acute injection of nesfatin-1 into the third brain ventricle reduces food consumption during the dark phase in rats.n Nesfatin-1 is also expressed in gastric X/A-like cells in the peripheral tissues. Nesfatin-1 has been reported to reduce gastric and duodenal motility and to delay gastric emptying.AimIn the present study, we investigated the effects of nesfatin-1 on gastrointestinal motility in conscious dogs.MethodsForce transducers were implanted onto the serosal surfaces of the gastric bodies, gastric antra, duodena, and jejuna of healthy beagle dogs, and gastrointestinal motility was monitored. We evaluated the effects of nesfatin-1 on gastrointestinal motility and on the circulating levels of nesfatin-1 in the fasted and fed states.ResultsThe intravenous administration of nesfatin-1 reduced gastric contractions and inhibited cyclical interdigestive migrating contractions in the fasted state. In the fasted state, circulating levels of nesfatin-1 tended to increase during late phase I. In addition, the kinetics of the circulating levels of nesfatin-1 were opposite to those of ghrelin during the fasted state.ConclusionsNesfatin-1 regulates gastrointestinal motility, and, in particular, it inhibits gastric contractions in the fasted state. Interdigestive migrating contractions may be regulated by interactions between nesfatin-1, ghrelin, and motilin.

The benefits of laparoscopically assisted distal gastrectomy for obese patients.

BackgroundIn Japan, the number of obese patients with gastric cancer is increasing. This study aimed to evaluate the advantages of laparoscopically assisted distal gastrectomy (LADG) for obese patients relative to those of conventional distal gastrectomy (DG).MethodsBetween January 2004 and June 2009, a total of 197 consecutive patients with gastric carcinoma underwent curative distal gastrectomy with Billroth 1 reconstruction in the Gunma University Hospital. The patients were assigned to undergo LADG (nxa0=xa0120) or DG (nxa0=xa077) according to the depth of tumor invasion and lymph node status. A body mass (BMI) of 25xa0kg/m2 or higher was defined as obesity, and the amounts of blood loss, the operating time, the number of lymph nodes dissected, and the postoperative complications experienced by obese and nonobese patients were compared.ResultsNone of the patients in the LADG group required conversion to laparotomy. In the DG group, significantly fewer lymph nodes were retrieved from the obese patients (22.5xa0±xa03.4) than from the nonobese patients (31.9xa0±xa02.0; Pxa0<xa00.05). However, among the obese patients, the number of lymph nodes retrieved did not differ significantly between the LADG and DG groups. In the LADG group, the obese patients had a longer operating time (206.6xa0±xa06.3 vs. 192.0xa0±xa03.1xa0min; Pxa0<xa00.05) and a greater estimated blood loss (158.2xa0±xa024.7 vs. 101.9xa0±xa010.4xa0ml; Pxa0<xa00.05) than the nonobese patients. The estimated blood loss correlated the surgical procedures and BMI. No significant difference in postoperative complications was noted between the obese and nonobese groups after each procedure.ConclusionsRelative to DG, LADG did not affect the radicality of the procedure for the obese patients, and there is no significant difference in the operating time. The estimated blood loss was significantly less for LADG than for DG. Surgeons should elect to perform LADG for obese patients with gastric cancer.