Ryuusuke Aihara

18F-Fluorodeoxyglucose Positron Emission Tomography: Useful Technique for Predicting Malignant Potential of Gastrointestinal Stromal Tumors

The malignant potential of gastrointestinal stromal tumors (GISTs) is difficult to diagnose before surgery because the diagnoses are based on tumor diameter and mitotic index. The progression of small GISTs is always observed because they do not seem to have malignant potential. 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a useful technique for assessing tumor activity. The objective of this study was to determine if FDG-PET is useful for predicting the malignant potential of gastric GISTs. Ten patients diagnosed with gastric GISTs participated. FDG-PET was performed on all of them before tumor resection. A whole-body image was initiated 40 minutes after the injection of 275 to 370 MBq FDG. FDG uptake was assessed by a standardized uptake value. All tumors had FDG uptake. There was a significant correlation between the FDG uptake and both the Ki67 index and the mitotic index but not the tumor diameter. The FDG uptake and malignant potential of gastric GISTs had a significant correlation. FDG-PET may be of considerable value for predicting the malignant potential of gastric GISTs before surgery. A gastric GIST with a high FDG uptake should be regarded as having malignant potential.

Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an experimental study of conscious dogs

Abstract  Ghrelin is a peptide that was discovered in endocrine cells of the stomach. However, its action in regulating the fasted and fed motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of an intravenous (i.v.) injection of canine ghrelin on the physiological fasted and fed motor activities in the stomach, duodenum, jejunum and colon of freely moving conscious dogs. An i.v. injection of canine ghrelin released growth hormone in a dose‐dependent manner; however, it did not stimulate the motor activity of the digestive tract in either the fasted or the fed state. Moreover, an i.v. injection of high‐dose canine ghrelin significantly reduced the motility index in the gastric body in the fasted state. Ghrelin did not accelerate gastric emptying, either. These results differ from previous reports dealing with rodents. It is significant that such results were obtained in research with dogs, which are larger animals.

Clinical significance of mucin phenotype, β-catenin and matrix metalloproteinase 7 in early undifferentiated gastric carcinoma

The aim of this study was to examine the clinical significance of mucin phenotypes of early undifferentiated gastric carcinoma, and to identify variables that might be used to select patients suitable for minimally invasive surgery.

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.

Gastric Schwannomas Show an Obviously Increased Fluorodeoxyglucose Uptake in Positron Emission Tomography: Report of Two Cases

Schwannomas are tumors originating from any nerve that has a Schwann cell sheath. Gastrointestinal (GI) schwannomas represent only 3% of all GI mesenchymal tumors. The stomach is the most common site of GI schwannomas, and schwannomas account for 0.2% of all gastric neoplasms. This report presents two cases of gastric schwannomas showing increased [18F]fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET; maximum standardized uptake value 7.10 and 6.05). Additional immunohistochemical staining of glucose transporter type 1 (GLUT1) and the autocrine motility factor (AMF) was conducted after the tumors were resected, to identify the mechanism that increased FDG uptake on PET. Immunohistochemical expression of AMF was positive in both cases, whereas GLUT1 was negative. Autocrine motility factor is also known as phosphoglucose isomerase. However, the mechanism by which FDG is accumulated in schwannoma cells is uncertain, and may be related to intracellular glycolytic activity.

The peptide hormone xenin induces gallbladder contractions in conscious dogs.

Abstract  Xenin is a 25‐amino acid peptide isolated from human gastric mucosa. The biological activities of xenin include modulating intestinal motility and affecting exocrine pancreatic secretion and gastric acid secretion. The physiological effect of xenin on the gastrointestinal tract, however, is incomplete. The objective of this study is to investigate the effects of xenin on the gastrointestinal tract motility of conscious dogs. Gastrointestinal tract and gallbladder contractions were monitored by chronically implanted force transducers. Synthetic xenin was injected intravenously during the interdigestive state with or without pretreatment with cholinergic blockers. The effects of xenin following cholecystectomy and truncal vagotomy were also investigated. Xenin induced gallbladder and jejunal contractions, although a dose‐dependent response was shown only with gallbladder contractions. These effects were inhibited by pretreatment with cholinergic blockers, but were not enhanced by truncal vagotomy. The jejunal contractions were completely inhibited by cholecystectomy. The only direct effect of xenin in terms of gastrointestinal motility was to induce gallbladder contractions in conscious dogs. The neural pathway mediating xenins action was cholinergic, but not the vagal. This novel finding indicates a new role of xenin.

Sudden bilateral sensorineural hearing loss as the presenting symptom of meningeal carcinomatosis of gastric cancer: Report of a case

Meningeal carcinomatosis is the diffuse infiltration of the meninges by metastatic carcinoma. A 62-year-old man presented with a sudden onset of profound hearing loss affecting both ears. Brain magnetic resonance imaging showed increased signal intensity on T1-weighted images of both vestibulocochlear nerves. Upper gastrointestinal endoscopy revealed a large type 3 gastric cancer, and the pathological diagnosis was poorly differentiated adenocarcinoma. Although combination chemotherapy with oral S-1 and weekly paclitaxel and radiation therapy were performed, the patient’s condition gradually worsened, and he eventually died 12 weeks after the onset of deafness. Isolated bilateral hearing loss is therefore considered to be a rare first manifestation of meningeal carcinomatosis.

Effect of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve to gastrointestinal function: an experimental study in conscious dogs.

Objective:To evaluate the effects of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve on gastrointestinal function. Summary Background Data:The operative procedure of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve is now in the spotlight in Japan with the goal of finding a function-preserving surgical technique. However, there has been no analysis of the effect of this type of surgery on gastrointestinal function. In this article, we describe the results of a fundamental experiment on distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve. Methods:Twenty conscious dogs were divided into 2 groups, each subdivided into 2 groups of 5: a normal intact dog group (NG) divided into 2 groups, with preservation (PNG) and resection (RNG; these dogs were truncally vagotomized including transaction of the celiac branch) of the celiac branch, and a gastrectomy dog group (GG) divided into 2 groups, with preservation (PGG) and resection (RGG) of the celiac branch. The motility of the dogs was recorded using strain gauge force transducers. The effects of the preservation of the celiac branch of the vagus nerve on gastrointestinal motility, gastric emptying, and pancreatic insulin release were evaluated. Results:The motility index of gastrointestinal motility with preservation of the celiac branch was higher than the motility index with resection of the celiac branch in fasted and fed of NG and GG. In gastric emptying, significant differences were found between the PNG and RNG but not between the PGG and RGG. In the fasted state for 80 minutes of the PNG and PGG, the serum insulin concentration reached a peak during the early phase III at 20 minutes in the gastric body and the antrum. Conclusions:This study has shown that it is effective to preserve the celiac branch of the vagus nerve for gastroduodenal motility, gastric emptying, and pancreatic insulin release after a gastrectomy.

Mucin phenotypic expression in early signet ring cell carcinoma of the stomach: its relationship with the clinicopathologic factors.

Gastric early-stage signet ring cell carcinoma (SIG) has been reported to have a lower rate of lymph node metastasis and a higher rate of favorable prognosis than other histological types. However, the development and progression mechanisms of early-stage SIG (early SIG) are controversial. This study examined the correlation between the mucin phenotype of early SIG and its clinicopathologic factors, particularly for the sake of less invasive surgery. Sixty-nine early SIGs were studied immunohistochemically with gastric mucin (M1 and MUC6) and intestinal mucin (MUC2). SIGs were classified into gastric (G), intestinal (I), gastrointestinal (GI), or unclassified (U) type. The intramucosal spreading patterns of SIG were investigated and then classified as either expansive or infiltrative. SIGs were classified into G-type (59.4%) and GI-type (40.6%). Neither the I- nor the U-type was observed. The GI-type expression correlated with the depth of tumor invasion in SIGs (P <0.05). In contrast, there was no increase in GI-type expression in relation to tumor size. Intramucosal infiltrative growth correlated with intestinal metaplasia (IM) of background mucosa of SIGs (P <0.01). There was no significant correlation between phenotypes and intramucosal spreading pattern. In conclusion, the GI-type expression of SIG is a clinically useful factor for predicting submucosal invasion. The findings of SIG surrounded with IM revealed the need to exercise great care in determining the surgical margin.

Prognostic significance of the expression of MUC1 and collagen type IV in advanced gastric carcinoma

Scirrhous gastric carcinoma is characterized by excessive deposition of collagen in the stroma. However, the clinical significance of this fibrosis of the stomach has not been clarified. The aim of this study was to examine the fibrotic mechanism in several histological types of gastric carcinoma, and the combination of MUC1 and collagen type IV as a possible predictor of patient survival.