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.     

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

Background  

In 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.     

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

Laparoscopy-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.     

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.     

Effect of duodenectomy on gastric motility and gastric hormones in dogs

OBJECTIVE: To 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. METHODS: Adult 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. RESULTS: After 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. CONCLUSIONS: Duodenectomy 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.