Mechanism of inhibitory effect of glucagon on gastrointestinal motility and cause of side effects of glucagon

Glucagon is commonly used during gastrointestinal examinations for the temporary inhibition of gastroduodenal movements. Three preparations of glucagon are now clinically available: those prepared by extraction from the pancreas (GL-P), by chemical synthesis (GL-S), and by genetic recombination (GL-G). The aim of this study was examine the mechanism of the inhibitory effect of glucagon on gastrointestinal motility and the cause of its side effects by comparing three glucagon preparations. In four conscious dogs, gastrointestinal contractions were monitored by means of chronically implanted force transducers. Each glucagon preparation (GL-P [15 μg/kg], GL-S [5, 15, 45 μg/kg], GL-G [15 μg/kg]), scopolamine butylbromide (0.4 mg/kg), or saline was administered intravenously 20 min after the termination of spontaneous phase III contractions, and blood samples were taken at 5- to 10-min intervals. Barium was administered into the stomach 10 min after the infusion of each drug. The arrival of a barium meal in the stomach immediately stimulated gastrointestinal contractions, and the barium meal was expelled into the duodenum and jejunum from the stomach. Intravenous injection of 15 μg GL-S first stimulated duodenal contractions that propagated to the jejunum, followed by strong inhibition of the barium-induced gastrointestinal contractions. This inhibitory effect of glucagon and the activity of the glucagon-induced duodenal contractions were dose-related. The inhibitory effects of GL-G and GL-S were stronger than that of GL-P. Blood glucose and plasma insulin concentrations were raised after intravenous injection of each glucagon preparation, but there was no difference among the three preparations and no dose relationship. The inhibitory effects of glucagon depend on the material purity and dose, and the inhibitory mechanism was independent of any effect on carbohydrate metabolism. Glucagon administration caused phase III-like contractions in the duodenum and jejunum, which may be responsible for the side effects of glucagon. (Received Jan. 8, 1998; accepted June 26, 1998)     

Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma

Background

The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.

Methods

Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs.

Results

On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis.

Conclusion

TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.

     

Malignant Transformation of the Mouse Anorectal Epithelium Induced by an Inoculated Human Cancer Cell Line

Four kinds of human cancer cell lines and one mouse cancer cell line were inoculated into the subepithelial area of the anorectum of female nude mice. Among the cell lines, two cell lines (KATO III and Lu 135) showed the potential enforcement of atypical changes in the adjacent mouse anorectal epithelium. Moreover, the submucosal invasion of the malignant transformed cells of the mouse epithelium was demonstrated in specimens obtained from three KATO III-inoculated mice. This exciting and novel phenomenon clearly demonstrates the need to change the present general concept of a single-cell origin of cancer tissue. This valuable and novel discovery may change the basis of oncology research while also providing new ideas for projects to investigate the mechanisms of carcinogenesis from several aspects such as molecular biology, cell biology, and pathology. Moreover, the novel experimental design itself is also extremely useful as a simple model for investigating the mechanisms of oncogenesis.     

Curative Resection Following Neoadjuvant Chemotherapy for Advanced Gastric Cancer With Preservation of a Right Gastroepiploic Artery Coronary Artery Bypass Graft: A Case Report

Recently, the right gastroepiploic artery (RGEA) has been used in coronary artery bypass graft (CABG) as an alternative arterial graft. Because of the improvement of prognosis after CABG, malignant diseases are more common in older patients. However, there is a serious problem in patients with gastric cancer after CABG with RGEA graft. In these patients, an interruption of coronary blood supply through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an appropriate strategy is very important to avoid risk while retaining the curability of the operation. We herein describe a 76-year-old Japanese man with advanced gastric cancer who underwent CABG using the RGEA. Abdominal computed tomography (CT) showed #6 lymph nodes (sub-pyloric lymph nodes) metastases surrounding the RGEA. We concluded that curative resection was impossible while preserving the RGEA and started combination chemotherapy using S-1 and cisplatin. After 2 courses of that, #6 lymph nodes were reduced extremely. Thereafter the patient underwent distal gastrectomy with regional lymph node dissection around the RGEA without excision of the RGEA. Histologically, there were no metastases in #6 lymph nodes. Neoadjuvant chemotherapy may be effective for preserving the RGEA graft in a patient with advanced gastric cancer after CABG.Key words: gastric cancer, CABG, RGEA bypass graft, neoadjuvant chemotherapyThe right gastroepiploic artery (RGEA) has been used in coronary artery bypass graft (CABG) surgery.^1,2 It is recognized as a reliable conduit with superior long-term patency.^3–5 The right gastroepiploic artery is mainly targeted to the right coronary artery because of the limitation of its length. According to the report of a Japanese association for coronary artery surgery, CABG was carried out in more than 0.1 million patients over a period of 7 years that ended in 2004, and the RGEA has been used in more than half of these patients.⁶ After CABG for either triple-vessel or left main disease, patients have a 5-year actual survival rate of 92.9% and a cardiac death-free rate of 97.8%.⁷ Long-term survival increases the opportunity for patients to develop malignant diseases. An increased incidence of gastric cancer after CABG with the use of RGEA has been reported.⁶ In these patients, an interruption of coronary blood supply through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an appropriate strategy is required to avoid risk while retaining the curative potential of the operation. We present a case of gastric cancer after CABG with the RGEA in which neoadjuvant chemotherapy led to curative operation while preserving the RGEA.     

An easy method for the intraluminal administration of peppermint oil before colonoscopy and its effectiveness in reducing colonic spasm

BACKGROUND: Systemic administration of a cholinergic blocking agent or glucagon is used to reduce spasms, but it is inconvenient and sometimes causes side effects. This study is an evaluation of the intracolonic administration of peppermint oil during colonoscopy for the control of colonic spasm. METHODS: Each patient in the treated group (n = 409) was given approximately 200 mL of the solution (a mixture of 8 mL of peppermint oil and 0.2 mL of Tween 80 per 1 L of water with 0.04% indigo carmine) by using a hand pump attached to the accessory channel of the colonoscope. Changes in patient posture were made to distribute the solution. The patients in the control group (n = 36) were given the solution without peppermint oil. RESULTS: A satisfactory spasmolytic effect was seen in 88.5% of the treated patients and in 33.3% of those in the control group (p<0.0001). No adverse effect was observed. The mean time to onset was 21.6 +/- 15.0 seconds, and the effect continued for at least 20 minutes. In patients with irritable bowel syndrome, efficacy was significantly lower (p < 0.0001). CONCLUSIONS: The intraluminal administration of peppermint oil by using a hand pump is a simple, safe, and convenient alternative to the systemic injection of a cholinergic blocking agent or glucagon during colonoscopy.     

Effect of Motilin on Endogenous Release of Insulin in Conscious Dogs in the Fed State

The aim was to investigate the insulin-releasing activity of motilin during and after feeding. A single intravenous bolus injection of motilin (0.01-0.3 microg/kg) dose-dependently stimulated endogenous release of insulin in the postprandial state. The insulin-releasing activity of motilin in the fed state was completely abolished by pretreatment with atropine or hexamethonium and was partly inhibited by ondansetron. Truncal vagotomy also greatly suppressed the motilin-induced insulin release. While phentolamine significantly enhanced insulin release in response to motilin, propranolol significantly inhibited this response in both states. The motilin-induced insulin release in the fed states was not accompanied by any changes in glucose concentrations. In conclusion, while the physiological significance remains unclear, these results indicate that physiological doses of motilin stimulate endogenous release of insulin via a vagally cholinergic muscarinic pathway, and that adrenergic and 5-hydroxytryptamine3 receptors are also involved in this response, in the dog.     

Results of multimodality therapy for squamous cell carcinoma of maxillary sinus

BACKGROUND: A wide variety of modalities, including surgery, radiation therapy, and chemotherapy, alone or in combination, have been used for the treatment of squamous cell carcinoma (SCC) of the maxillary sinus to obtain better local control and maintain functions. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1987 to 1999, 33 patients with SCC of maxillary sinus were treated at the Department of Otolaryngology-Head and Neck Surgery, University of Tokyo Hospital. The treatment consisted of 30-40 grays (Gy) of preoperative radiotherapy with concomitant intraarterial infusion of 5-fluorouracil and cisplatin followed by surgery and 30-40 Gy of postoperative radiotherapy, for tumors without skull base invasion. For tumors invading the skull base, preoperative systemic chemotherapy with or without radiotherapy was performed, instead of intraarterial chemotherapy, then followed by skull base surgery. The surgical procedures varied according to the extent of tumor. Results were compared with those of the 108 patients treated in our hospital from 1976 to 1982. RESULTS: Partial maxillectomy was performed in 2 T2 patients and 12 T3 patients. Total maxillectomy was performed in 1 T2 patient, 3 T2 patients, and 7 T4 patients. Skull base surgery was performed in eight T4 patients. Orbital content and hard palate were preserved in 22 patients and 18 patients, respectively. The overall 5-year survival rates were 86% in T 3 patients and 67 % in T4 patients, respectively. CONCLUSIONS: Our multimodal treatment has provided favorable local control and survival outcome with good functional results.     

Circulating soluble Fas ligand in patients with gastric carcinoma

BACKGROUND: The Fas/Fas ligand (FasL) system is involved in cancer cell death induced by the immune system. Most of the tumors may escape the host immune attack by imitating themselves as immune-privileged sites by overexpressing FasL. FasL is synthesized as a membrane-bound protein that can be cleaved to the soluble isoform (sFasL). The objectives of this work were to determine whether the serum concentrations of sFasL in patients with gastric carcinoma were correlated with clinicopathologic features and survival rates. METHODS: The authors examined the circulating sFasL concentration in 43 healthy people and 166 primary gastric carcinoma patients at the time of diagnosis by enzyme linked immunoadsorbent assay. The results were categorized by clinical and histopathologic variables. RESULTS: The serum sFasL levels of healthy subjects were all less than 0.1 ng/mL. Among the 166 gastric carcinoma patients, the median concentration of sFasL was 0.04 ng/mL. There were no significant differences between the healthy controls and the gastric carcinoma patients group (P = 0.738). The sFasL levels were significantly increased in patients with gastric carcinoma in a manner reflective of the disease stages such as the depth of tumor invasion, lymph node metastasis, and distant metastasis. The authors determined the cutoff value (0.08 ng/mL) as a 90th percentile of healthy controls. The survival analysis demonstrated that patients with high sFasL levels had a worse prognosis than those with low levels (P < 0.001). Multivariable analysis confirmed that the sFasL concentration was an independent prognostic indicator of overall survival (P = 0.041). CONCLUSIONS: Our results indicated that sFasL concentrations could not be a new marker for early detection of gastric carcinoma but a prognostic tumor marker for the assessment of the progression of advanced gastric carcinoma.     

Idiopathic Omental Bleeding: Report of a Case

We report a case of idiopathic omental bleeding in a 27-year-old man who was brought to our hospital after the sudden development of intermittent abdominal pain, nausea, and fainting. Computed tomography showed intra-abdominal fluid and emergency laparotomy revealed a hemorrhagic mass in the omental bursa, which was excised. The patient was successfully treated and a diagnosis of idiopathic omental bleeding was made.