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Biomedical subjects

S Matsuno

Publications and source records attributed to S Matsuno.

At least 55 records · Page 3Linked to original sources
PubMed2001

Trends in treatment for pancreatic cancer.

Although surgical resection is considered to be the only approach that offers a possibility of cure to patients with pancreatic cancer, the prognosis of the disease has not been improved markedly by any surgical procedures in the past 20 years. Large-scale randomized prospective clinical trials are being conducted in the United States and Italy, comparing standard lymph node dissection with extended lymph node dissection. Although preoperative chemoradiation has various advantages in the treatment of pancreatic cancer, it does not contribute to its downstaging and eventual cure. The combination of leucovorin, 5-fluorouracil (5-FU), and extracorporeal irradiation, however, has been proven to improve the patient's quality of life (QOL). Palliative surgery still requires further research in areas such as the examination of morbidity rates and the duration of bypass effects, now that laparoscopic and endoscopic surgery have both been well developed. Recent biological research has revealed the mechanisms of the carcinogenesis and the progression of pancreatic cancer, and, against this background, we assume that more effective trials will be conducted soon. Immunotherapy with dendritic cells, as well as gene therapy with mutant adenovirus, has already been employed clinically. Pancreatic cancer therapy is now facing new prospects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Cytokine modulation in acute pancreatitis.

The clinical manifestations of acute pancreatitis (AP) vary significantly from mild to lethal in form, the severity of the disease being largely determined by the actions of various kinds of inflammatory mediators, including cytokines, reactive oxygen species, proteolytic enzymes, and lipids, as well as gaseous mediators. Despite increasing knowledge implicating the involvement of cytokines in the progression of AP, no clinical trials pertaining to cytokine modulation have been performed so far. Progress in intensive care technologies has contributed to the improvement of mortality and morbidity rates in severe AP in the past decade; however, it appears to be reasonable for clinicians to "line up their sights" on the modulation of cytokines as a direct treatment. In contrast to the large body of experimental studies demonstrating the beneficial effects of cytokine modulation on the amelioration of the disease, direct extrapolation from these successful experiments to the clinical situation seems to be extremely difficult.

Acute Disease↗
PubMed2001

Continuous regional arterial infusion (CRAI) therapy reduces the mortality rate of acute necrotizing pancreatitis: results of a cooperative survey in Japan.

We evaluated the usefulness of continuous regional arterial infusion (CRAI) of protease inhibitors and antibiotics in 156 patients with acute necrotizing pancreatitis (ANP) collected in a cooperative survey carried out in 1997 in Japan. The overall mortality rate was 18.6%, and the frequency of infected pancreatic necrosis was 12.8%. There was no significant difference in mortality rates between patients who received the protease inhibitor via CRAI and the antibiotics intravenously (group A) and patients who received both the protease inhibitor and the antibiotics via CRAI (group B), but the frequency of infected pancreatic necrosis was significantly lower in group B (7.6%) than in group A (23.5%). The mortality rate in patients in whom CRAI therapy was initiated within 48 h after the onset of ANP (11.9%) was significantly lower than that in patients in whom CRAI therapy was initiated more than 48 h after the onset (23.6%). These results suggested that CRAI of both protease inhibitors and antibiotics was effective in reducing mortality and preventing the development of pancreatic infection in ANP when initiated within 48 h after the onset of ANP.

Adult↗
PubMed2001

Hemodynamic patterns of phosphatidylcholine hydroperoxide and hyaluronic acid during hepatic ischemia-reperfusion.

We investigated the hemodynamic pattern of serum hyaluronic acid (HA) and compared it with that of plasma phosphatidylcholine hydroperoxide (PCOOH) in terms of a convenient parameter of reperfusion injury. Using pig models, we designed two continuous ischemia groups, prepared by blockage of the blood flow at the hepatic hilum for 10 or 30 min. A discontinuous ischemia model was prepared by repeating the 10-min ischemia procedure, followed by 10 min of reperfusion, to a total ischemia period of 30 min. The PCOOH level started to increase just after reperfusion and reached the peak at 90 min, followed by a gradual decline after 6 h. The HA level increased rapidly in the continuous ischemia groups, starting immediately after ischemia onset until immediately before reperfusion, followed by a gradual decrease during up to 6 h of reperfusion. The HA levels in the three groups were almost normalized after 90 min of reperfusion, when the PCOOH level reached the peak. These results indicated that the plasma PCOOH level is a useful parameter for predicting the onset and progress of reperfusion injury in its initial stages.

Animals↗
PubMed2001

Early microcirculatory derangement in mild and severe pancreatitis models in mice.

An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte-endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability.

Acute Disease↗
PubMed2001

Laparascope-assisted versus conventional restorative proctocolectomy with rectal mucosectomy.

To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis compared with conventional procedures, we retrospectively analyzed the results of the two procedures as follows: Eleven patients including five patients with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal J-pouch anal anastomosis at our department from June 1997 to November 1999. This laparoscope-assisted colectomy (LAC) group was then compared with a group of 13 patients who had undergone conventional ileal pouch anal anastomosis using a standard laparotomy from 1986 to 1997. The median operative time of the LAC group was 8h 23min, which was 81 min longer than that of the standard colectomy (SC) group. The number of days during which eating was prohibited were similar in the two groups but the median postoperative hospital stay was significantly shorter in the LAC group (24.1 days). In the LAC group, the small incisions showed better cosmetic results and there was also a remarkable reduction in the degree of postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis can be employed widely in patients with FAP and also in selected patients with UC.

Adenomatous Polyposis Coli↗
PubMed2001

Transverse colonic cancer presenting as an anterior abdominal wall abscess: report of a case.

An 81-year-old man who had been aware of a right anterior abdominal mass for 1 week was admitted to our hospital on July 3, 1999, after the mass had perforated and was secreting mucinous purulent material. Computed tomography clearly showed an anterior abdominal wall abscess and a large intraabdominal tumor that contained a fistula-like structure. Barium enema revealed an apple-core sign at the transverse colon, with a fistula that connected the colon to the abscess cavity. Transverse colonic cancer complicated by an anterior abdominal wall abscess was diagnosed, and an extended right hemicolectomy was performed. We did not perform en bloc excision of the full thickness of the anterior abdominal wall, including the abscess, because the defect was determined to be too large to repair. Thus, when curative resection is not feasible, as in our patient, resection of the primary tumor with en bloc partial resection of the adherent parietal wall should be performed if possible, as this procedure has the potential to improve the postoperative quality of life of the patient.

Abdominal Abscess↗
PubMed2001

Malignant pheochromocytoma with hepatic metastasis diagnosed 10 years after a resection of the primary incidentaloma adrenal lesion: report of a case.

A 40-year-old woman developed hepatic tumors 10 years after a resection of pheochromocytoma of the left adrenal gland. Computed tomography showed a round tumor measuring about 35mm in diameter at segment V of the liver (Couinaud's classification), and magnetic resonance imaging showed another tumor measuring about 5mm at segment V-VIII of the liver. The results of the endoscopic examination of her upper gastrointestinal tract and barium enema were normal. Owing to a suspected hepatic metastasis of malignant pheochromocytoma, a right lobectomy of the liver was performed. Postoperatively, [131I]metaiodobenzylguanidine scintigram and computed tomography showed no other residual tumors nor metastasis. The present case suggests that a long-term follow-up only by endocrinological examinations is insufficient to find newly developed metastatic foci, while routine diagnostic imaging at frequent intervals is necessary in cases of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed2001

Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits.

Epidemiological studies have shown that cigarette smoking is a major cause of atherosclerosis. Oxidants as well as nicotine in cigarette smoke have been implicated in atherogenesis. To clarify the mechanism involved, we examined the chronic effects of nicotine and nicotine-free cigarette smoke extracts (CSE) on oxidative modification of low-density lipoprotein (LDL) in the plasma of Watanabe heritable hyperlipidemic rabbits and atherogenesis in the aorta. CSE was prepared by bubbling the gas phase of smoke (1 ml/three cigarettes) into phosphate buffer saline, and 3 ml of this CSE was injected daily into the ear vein of the rabbit for five months. The rabbits treated with CSE showed an increase in lipid peroxide levels, estimated as thiobarbituric acid reactive substances (TBARS), with a corresponding decrease in vitamin E levels in the plasma. They also showed enhanced oxidative modification of LDL, assessed by anion-exchange HPLC, incorporation into macrophages and measurement of TBARS. These events could be efficiently prevented by administering vitamin E (150 mg/kg/day, p.o.). Nicotine alone (0.5 mg/kg/day, s.c.) led to a temporary increase in the plasma triglyceride level. At the end of the experiment, CSE but not nicotine had caused progression of atherosclerotic lesions together with accumulation of cholesteryl ester in the thoracic aorta, while vitamin E had significantly prevented such atheromatous formation. These results indicate that oxidants in CSE can promote the development of atherosclerosis through oxidative modification of plasma LDL, particularly in hypercholesterolemia, and offer evidence for increased vitamin E utilization in smokers.

Animals↗
PubMed2001

Intraduodenal and intrajejunal administration of the herbal medicine, dai-kenchu-tou, stimulates small intestinal motility via cholinergic receptors in conscious dogs.

The aim of the present study was to study the effect and mechanism of action of intraduodenal and intrajejunal dai-kenchu-to, an herbal medicine clinically effective for uncomplicated postoperative adhesive intestinal obstruction, on upper gastrointestinal motility. Five mongrel dogs were equipped with four strain-gauge force transducers on the antrum, duodenum, and proximal and distal jejunum to measure contractile activity. Dai-kenchu-to (0.5, 1.5, and 3.0 g) was administered into the duodenal or proximal jejunal lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intraduodenal and intrajejunal dai-kenchu-to-induced contractions was studied. Plasma motilin was measured by specific radioimmunoassay. Intraduodenal and intrajejunal dai-kenchu-to induced phasic contractions in the duodenum and proximal jejunum, respectively, and those contractions migrated distally. Phasic contractions induced by intraduodenal and intrajejunal dai-kenchu-to were inhibited by atropine and hexamethonium at all sites. Plasma motilin was not affected by dai-kenchu-to. Intraduodenal and intrajejunal dai-kenchu-to stimulates upper gastrointestinal motility at and distal to the administration sites through cholinergic receptors.

Animals↗
PubMed2001

LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers.

BACKGROUND & AIMS: One approach to the development of targeted cancer chemotherapy exploits increased uptake of the agent into neoplastic cells. In this scenario, higher concentrations of the agent in cancer cells are responsible for differential killing, whereas the low concentration in normal human cells decreases side effects. The aim of this study was to isolate an organic anion transporter that is weak in normal cells, but abundantly expressed in cancer cells, to deliver the anticancer drugs to the cells. METHODS: A human liver complementary DNA (cDNA) library was screened with liver-specific transporter (LST)-1 cDNA as a probe. Northern blot analyses were performed using the isolated cDNA (termed LST-2). An LST-2-specific antibody was raised, and immunohistochemical analyses including immunoelectron microscopy were performed. Xenopus oocyte expression system was used for functional analysis. We also established a permanent cell line that consistently expresses LST-2 to examine the relationship between methotrexate uptake and sensitivity. RESULTS: The isolated cDNA, LST-2, has 79.7% of overall homology with human LST-1. LST-2 exclusively expressed in the liver under normal conditions and its immunoreactivity was highest at the basolateral membrane of the hepatocytes around the central vein. Although its weak expression in the liver, LST-2 is abundantly expressed in the gastric, colon, and pancreatic cancers. On the other hand, the LST-1 was only detected in a hepatic cell line. LST-2 transports methotrexate in a saturable and dose-dependent manner. Furthermore, introduction of the LST-2 gene into mammalian cells potentiates sensitivity to methotrexate. CONCLUSIONS: LST-2 is one of the prime candidate molecules for determining methotrexate sensitivity and may be a good target to deliver anticancer drugs to the gastrointestinal cancers.

Amino Acid Sequence↗
PubMed2001

Effect of glucagon, glicentin, glucagon-like peptide-1 and -2 on interdigestive gastroduodenal motility in dogs with a vagally denervated gastric pouch.

BACKGROUND: We previously reported that inhibition of gastric motility and hypertrophy of the small intestinal mucosa were observed after ileo-jejunal transposition which induced hypersecretion of enteroglucagon. Our aim was to study the effect of four enteroglucagon-related peptides (glucagon, glucagon-like peptide (GLP)-1, -2 and glicentin) on gastroduodenal motility and their mechanisms of action. METHODS: The effect of these four peptides on motilin-induced interdigestive contractions was studied in dogs with vagally denervated gastric pouches equipped with four strain gauge force transducers on the pouch, gastric body, antrum and duodenum. Whether or not nitric oxide synthase inhibitor or phentolamine and propranolol reverses the inhibitory effect of those peptides was also studied. RESULTS: Glucagon inhibited contractions in the pouch and stomach but had no effect on duodenal contractility. GLP-1 inhibited contractions at all sites. GLP-2 inhibited contractions in the pouch but did not affect motility in the neurally intact gastroduodenum. Glicentin had no effect on contractions at any site. Pretreatment with either a nitric oxide synthase inhibitor or phentolamine and propranolol reversed the inhibitory effect of glucagon, GLP-1 and GLP-2 on contractions in the pouch, but did not alter the inhibitory effect of glucagon and GLP-1 on motility in the neurally intact stomach and duodenum. CONCLUSIONS: These results suggest that the effects of four peptides on gastroduodenal motility differ, and changes occur in the enteric neural modulation of motor activity after chronic surgical extrinsic denervation.

Animals↗
PubMed2001

Role of intraoperative insulin monitoring in surgical management of insulinoma.

BACKGROUND AND PURPOSE: Precise localization and surgical excision is the therapeutic strategy for insulinomas. However, it is often difficult to localize the insulinomas, because of their small size. Surgeons may not localize and remove all of them together, particularly in patients with multiple insulinomas. We reviewed our experience to confirm the efficacy of blood glucose and intraoperative immunoreactive insulin (IRI) monitoring for surgical management of insulinomas. PATIENTS AND METHODS: Thirty-nine patients with insulinoma were surgically treated in our department. Perioperative blood glucose monitoring was performed in 14 patients, intraoperative quick IRI assay of the peripheral blood in 10 patients, and assay of a portal sample in 4 patients by an IMX analyzer. RESULTS: Rebound response of blood glucose to insulinoma removal was not always noted (8/14; 57%). Seven of ten patients showed a decrease of peripheral serum IRI levels within 15 minutes after removal of the insulinoma. The other two patients showed a rebound response of peripheral blood glucose or portal IRI. All the patients who had intraoperative monitoring of peripheral blood and peripheral and portal IRI had no recurrent insulinoma syndrome after surgical removal of their insulinomas. CONCLUSION: Combined monitoring of peripheral blood glucose and peripheral and portal IRI are helpful in the surgical management of insulinomas, as they can indicate that no insulinoma remains.

Adolescent↗
PubMed2001

Continuous regional application of protease inhibitor in the treatment of acute pancreatitis. An experimental study using closed duodenal obstruction model in dogs.

In clinical settings, the effectiveness of protease inhibitors in the treatment of acute pancreatitis has been still controversial. With the concept that sufficient tissue concentration of protease inhibitor in the pancreas has to be included to achieve its potent inhibitory effect, we applied a continuous regional intra-arterial (CRI) application of low-molecular-weight protease inhibitor, nafamostat mesilate (FUT-175), for closed duodenal loop obstruction model in mongrel dogs. The use of CRI application led to a higher concentration of FUT-175 in the pancreatic tissue (4,453 +/- 758 ng/g) when compared with that applied intravenously (905 +/- 48 ng/g). Consequently, pancreatic parenchyma in CRI application animals was remarkably preserved, as assessed by the lower extent of pancreatic necrosis (12.4 +/- 2.6% in CRI vs. 25.6 +/- 1.9% in intravenous). Additionally, the elevation of trypsin-like activity in the pancreas was significantly inhibited in CRI animals. Based on these findings, the dose as well as the route of protease inhibitors should be carefully considered to achieve its beneficial effect.

Animals↗
PubMed2001

Benefit of continuous regional arterial infusion of protease inhibitor and antibiotic in the management of acute necrotizing pancreatitis.

Although we have reported the beneficial effect of continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic on acute necrotizing pancreatitis (ANP), the optimal timing of the initiation of CRAI therapy has not been clarified. The present study was conducted to evaluate whether the difference of the timing of CRAI therapy may affect the clinical course and outcome in ANP. 73 patients with ANP were stratified into three groups according to the interval between the onset and initiation of CRAI therapy as follows: group I (32 patients in whom CRAI therapy was initiated within 48 h after the onset); group II (22 patients in whom CRAI therapy was initiated between 48 and 72 h after the onset), and group III (19 patients in whom CRAI was initiated more than 72 h after the onset). The mortality rate was 3.2% in group I, 9.1% in group II, and 26.3% in group III. The mortality rate was significantly low in group I compared with that in group III. The frequency of respiratory failure in group I was also significantly low compared with that in group III. CRP and APACHE II score were reduced rapidly in both groups I and II after the initiation of CRAI therapy. These results suggested that the optimal timing of CRAI therapy in ANP should be considered to be within 72 h after the onset.

APACHE↗