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Biomedical subjects

S Isaji

Publications and source records attributed to S Isaji.

At least 37 records · Page 2Linked to original sources

Therapeutic efficacy of continuous arterial infusion of an antibiotic and a protease inhibitor via the superior mesenteric artery for acute pancreatitis in an animal model.

The major cause of death in acute pancreatitis is severe infection owing to bacterial translocation. As a new strategy, we investigated the effects of continuous intra-arterial infusion of an antibiotic (imipenem) or protease inhibitor (nafamostat mesylate) via the superior mesenteric artery (SMA) on bacterial translocation in acute pancreatitis. Infusion of saline (group I), nafamostat mesylate (group II), or imipenem (group III) was started 6 hours after inducing acute pancreatitis in dogs by infusing autologous gallbladder bile into the main pancreatic duct. The survival rate in group III was significantly improved compared to group I(100 vs. 30% at 24 hours), and bacterial infection of the peritoneal fluid, mesenteric lymph nodes, and pancreas was completely prevented in group III. Intestinal damage assessed by light and scanning electron microscopy and by biochemical parameters (mucosal protein content and myeloperoxidase activity) was also significantly mitigated in group III, which showed milder pancreatic necrosis as well. There was little beneficial effect in preventing bacterial translocation in group II, although the survival rate at 24 hours (70%) was improved. Continuous arterial infusion of an antibiotic via the SMA is effective in mitigating intestinal mucosal damage and preventing bacterial translocation in acute pancreatitis, thereby improving survival.

Acute Disease↗

A case of mixed acinar-endocrine carcinoma of the pancreas discovered in an asymptomatic subject.

A 50-yr-old Japanese man was found to have a hypoechoic mass 3 cm in diameter in the pancreatic head on an ultrasonography (US) examination without symptoms. A computed tomography (CT) scan demonstrated a 3-cm solid mass in the pancreatic head, and it was more clearly delineated as a low-density area on enhanced CT. Angiography showed a tumorlike stain, 3 cm in size, in the pancreatic head. The preoperative diagnosis was "special type of pancreatic tumor such as acinar cell carcinoma or non-functioning islet cell tumor." The patient was treated by pylorus-preserving pancreatoduodenectomy. Histological, immunohistochemical, and electron-microscopic studies of the surgical specimen led to a definitive diagnosis of a mixed acinar-endocrine carcinoma. The patient is currently well, with no signs of tumor recurrence, 18 mo after the operation. Our search of the Japanese and English-language literature retrieved only 15 well-documented cases of mixed acinar-endocrine carcinoma. Imaging in the reported cases revealed features of either acinar cell carcinoma or islet cell tumor, or both, which can may be detected even in small tumors more easily than conventional invasive ductal carcinoma of the pancreas because the detectability of this rare tumor on US and CT seems to be good.

Carcinoma↗

[Evaluation of classification of pancreatic cancer by the Japan Pancreas Society and Union Internationale Contre le Cancer and proposal for a new international classification].

Different classification systems of pancreatic cancer by the Japan Pancreas Society (JPS, 1996) and Union Internationale Contre le Cancer (UICC) (1997), both of which are based on the TNM system, have been hampering the exchange of data between Japan and Western countries. In the present study, both classifications were assessed using data from 67 patients with invasive ductal carcinoma of the pancreatic head who underwent resection at our clinic. We also propose a new TNM classification and stage grouping system that draws on the merits of both. The results showed that UICC stage grouping did not reflect outcome well, while the JPS system predicted outcome much better. The prognostic value of tha T category is sufficiently reliable in both classifications, but the major drawback of the JPS system is its complex structure and difficult handling. To meet the ideal standard for an international classification system, we propose a new classification: the T category is a minor modification of that of the UICC, and the N category is a modification of that of the JPS for much simpler grouping. Based on the data from our 67 resected patients cases, our new staging system reflects the outcome in the four stages well. Our new classification system may improve the staging classification and lead to the establishment of a more practical and universal staging system for ductal carcinoma of the pancreas.

Humans↗

Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus.

BACKGROUND: Esophageal carcinoma is one of the most lethal tumors. Therefore, it is important to identify prognostic factors for patients with this disease. The objective of this study was to clarify the relation between clinicopathologic and biologic factors in esophageal carcinoma and to determine the prognostic significance of different biologic factors. METHODS: DNA ploidy pattern, Ki-67 labeling index (LI), and cyclin D1 and p53 protein expression were examined and detailed pathologic examinations were conducted on tumors from 53 patients (46 males and 7 females with a mean age of 66 years [range, 47-85 years]) with surgically resected esophageal squamous cell carcinoma and the prognostic value of these factors was evaluated. RESULTS: Of the 53 esophagus carcinomas examined, 26 (49%) were classified as DNA diploid. The mean Ki-67 LI was 45 +/- 4. 9% (range, 10.5-86.1%). p53 expression was detected in 38 of the carcinomas (71.7%) and cyclin D1 expression was detected in 35 (66%). Various prognostic factors were examined using the Cox stepwise regression model, four of which were found to correlate with overall survival: tumor size (P = 0.0346), lymph node status (P = 0.0384), Ki-67 LI (P = 0.0161), and p53 expression (P = 0.001). Lower Ki-67 LI and a lower rate of p53 expression were detected in the long term survival group (> 3 years) compared with the short term survival group (P = 0.00045 and P = 0.0023, respectively). CONCLUSIONS: The biologic factors of Ki-67 LI and p53 expression, as well as clinicopathologic factors, may be used as independent prognostic factors for patients with esophageal carcinoma. However, the results of the current study do not support cyclin D1 expression as a prognostic factor.

Aged↗

Hepatocellular carcinoma complicated by gastrointestinal hemorrhage caused by direct tumor invasion of stomach.

A 65-year-old man with multiple hepatocellular carcinoma (HCC) underwent intra-hepato-arterial chemotherapy (IHAC) through an implantable port over a period of 10 months after transcatheter arterial embolization (TAE) had been performed three times. TAE was performed twice more, and radiotherapy (total dose, 30 Gy; given over a 3-week period) was given for progressive disease in the lateral segment of the liver. Three months after the radiotherapy had finished, the patient suddenly developed melena. Diagnostic imaging revealed gastrointestinal (GI) hemorrhage from HCC invading the stomach, and total gastrectomy and lateral segmentectomy of the liver were performed because the bleeding could not be controlled. The resected specimen disclosed a centrally necrotic tumor that had invaded the lesser gastric curvature and perforated into the lumen. Pathology examination revealed that the HCC had expansively invaded the gastric mucosa, resulting in exposure in the lumen. The possible mechanisms of direct GI invasion by HCC are briefly discussed, with a review of the literature. GI bleeding secondary to involvement by HCC is rare. The enteric radiation injury seems to have been largely responsible for the GI bleeding in this patient.

Aged↗

Clinicopathological features and outcome of hepatic resection for intrahepatic cholangiocarcinoma in Japan.

As a result of an increasing number of studies on the surgical treatment of intrahepatic cholangiocarcinoma (ICC), knowledge of its biological characteristics has been accumulating. We analyzed the clinicopathological features and outcome of 36 of 48 surgical patients with histologically proven ICC (75.0%) who underwent hepatic resection between March 1979 and July 1998. According to tumor location, 12 patients had the central type and 24, the peripheral type. The incidence of portal vein tumor thrombus and lymph node metastasis was higher in the central type than in the peripheral type. All 12 patients with the central type had stage IV disease, and none of them underwent complete resection, whereas 12 of the 24 patients with peripheral type tumors had stage IV disease; complete resection was achieved in 12 of the 24 patients with peripheral type tumors (50%). Outcome after resection was significantly poorer in the patients with the central type. The macroscopic type of lesion in the resected specimens was the mass-forming type in 15 patients (41.7%), the mass-forming + periductal-infiltrating type in 15 patients (41.7%), the periductal-infiltrating type in 3 patients (8.3%) and the intraductal growth type in 3 patients (8.3%). The macroscopic tumor type was associated with mode of tumor spread and outcome. All 3 patients with the intraductal growth type are alive without tumor recurrence 26-138 months after surgery. The survival rate was much higher in the patients with the mass-forming type than in those with the mass-forming + periductal-infiltrating type. Importantly, the outcome in the 17 patients who underwent resection for stage IV-B disease and who accounted for 47.2% of patients with resection in the present series was very poor, almost the same as that in the 12 patients who did not undergo resection. By selecting patients based on the biological characteristics of the tumor and taking into account patients' quality of life, complete surgical resection can be performed safely and is associated with long-term survival.

Aged↗

Prospective study of a protocol for selection of treatment of acute pancreatitis based on scoring of severity.

BACKGROUND/AIM: Since July 1994, we have been conducting a prospective study of a protocol for selection of treatment of acute pancreatitis based on scoring of severity. METHODS: From July 1994 to June 1998, 56 patients with acute pancreatitis were enrolled in this study. The protocol employed was based on the results of our retrospective study. On admission, the prognosis score (scoring of severity of acute pancreatitis based on the criteria of the Ministry of Health and Welfare of Japan) and APACHE II score were calculated, and early treatment was selected according to the protocol. RESULTS: All of the 26 patients with gallstone pancreatitis and 28 of 30 patients with non-gallstone pancreatitis were successfully treated and had good outcome. There were 2 deaths in non-gallstone pancreatitis. In selection of early treatment according to the scoring of severity, we suggested that when the prognosis score is 2 or more and the APACHE II score of 8 or more, gallstone pancreatitis should be treated by biliary drainage, and non-gallstone pancreatitis by peritoneal lavage. When infected pancreatic necrosis is exhibited, surgery is indicated. CONCLUSION: Our new management protocol for acute pancreatitis based on the prognosis score and APACHE II score appear to be useful for accurately scoring severity and selecting the treatment methods.

Acute Disease↗

Effect of IS-741 (a new synthetic antiinflammatory agent) on acute necrotizing pancreatitis in dogs. Significance of its inhibitory effect on cytosolic phospholipase A2.

IS-741, a new synthetic anti-inflammatory agent, is known to have some inhibitory effect on cytosolic phospholipase A2 (cPLA2), an enzyme which hydrolyzes cellular phospholipids, liberating fatty acids and lysophospholipids and providing the precursor substrates for the biosynthesis of eicosanoids and platelet-activating factor. cPLA2 is therefore an attractive target for the development of novel therapies. During infusion of lactated Ringer's solution at a rate of 10 ml/kg/h, acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. The dogs were then divided into two groups: group A (nontreatment), no treatment during the experiment, and group B (IS-741), intravenously injected with IS-741 at 6 and 30 h after induction of acute pancreatitis. As a result, the survival rate was significantly higher in group B than in group A. Mean arterial pressure and PaO2 were well maintained in group B as compared with group A. The NAG index, which is known to be markedly increased in renal tubular damage, was significantly lower in group B than in group A. Histological examination of the pancreas, lung, and kidney in group B showed milder changes than in group A. cPLA2 activity in the pancreas, lung and renal cortex was much lower in group B than in group A, but sPLA2 activity in these tissues did not differ significantly between the two groups. In conclusion, IS-741 exerts a potentially therapeutic effect on experimental acute pancreatitis by mitigating the degree of damage in the pancreas, lung, and kidney. The inhibitory effect of IS-741 on cPLA2 may contribute to one of the antiinflammatory mechanisms of actions of this agent.

Animals↗

Modified standard pancreaticoduodenectomy for the treatment of pancreatic head cancer.

Since 1980 extended surgery has been used to treat pancreatic cancer in many institutions in Japan in the hope of achieving curative resection and a good outcome. The resection rate increased, but the final outcome was unsatisfactory, and the question of postoperative quality of life (QOL) following extended surgery has instead become the central issue. During the past 22 years (October 1976 to June 1998) 169 of the 188 patients with invasive pancreatic ductal carcinoma at Mie University Hospital were treated surgically. A standard operation was performed in the early period (October 1976 to April 1981, n = 34), an extended operation was performed in the middle period (May 1981 to March 1993, n = 100), and a modified standard operation was performed in the late period (April 1993 to June 1998, n = 35). 'Standard operation' means pancreaticoduodenectomy (PD) with D1 lymph node dissection (regional), and 'extended operation' means PD with D2-D3 lymph node dissection. Our 'modified standard operation' consists of PD with lymph node dissection limited to the anterior pancreaticoduodenal (APD), posterior pancreaticoduodenal (PPD), pyloric (PY), hepatoduodenal ligament (HDL), common hepatic artery (CH) and right half of the superior mesenteric (SM) nodes. Thus, the extent of lymph node dissection in the modified standard procedure lies between the level in the standard and extended procedure, but the PD is the same, with only slight modification in the reconstruction procedure. We consider the standard operation to be a less curative procedure and the extended operation to be a very stressful procedure and accordingly we have modified it (modified standard operation) in our recent cases out of consideration for patients' QOL. We found that postoperative QOL and survival were much better in the late period than in the early and middle periods.

Humans↗

Adenocarcinoma arising in a tailgut cyst: report of a case.

We report herein the unusual case of a 66-year-old woman found to have adenocarcinoma arising in a tailgut cyst. The patient had been observed for 6 months following the discovery of a presacral cystic mass measuring 10 x 9 cm for which she had refused surgery. The serum tumor marker, carcinoembryonic antigen, became slightly elevated, and diagnostic imaging distinctly revealed a tumorous lesion with papillary projection into the cyst lumen. The cystic mass was then excised through the transsacral approach. The pathological findings were compatible with moderately differentiated adenocarcinoma arising in a tailgut cyst. This entity is extremely rare, and only six cases, including our own, have been reported in the English literature. Early complete excision is advised because it is almost impossible to determine for certain whether presacral cystic masses are benign or malignant prior to surgery.

Adenocarcinoma↗

Staging and extended resection for pancreatic cancer.

Extended surgery is being widely performed to treat pancreatic cancer in Japan, but it has not been evaluated in the same way as in other countries. We, therefore, compared the Japanese Stage Classification (JPN-SC) with the Union Internationale Contre le Cancer Stage Classification (UICC-SC) in the surgical cases of pancreatic cancer treated in our department and then assessed the results of extended resection and associated problems. Problems existed in the resection rates and actuarial survival rates in stages II and III in the UICC-SC, and the JPN-SC was found to reflect more accurately the outcome. On the other hand, although improvements in curative resection and actuarial survival rate have been achieved as a result of extended resection in Japan, the outcome in JPN-SC surgical stage IVb and highly advanced cases in which these resections proved to be noncurative even though they were classified as surgical stage IVa was extremely poor. In the future, it will be necessary to decide on a single-stage classification that is accepted throughout the world and to conduct prospective studies matched to the degree of tumor progression.

Humans↗

Stage classifications of pancreatic cancer: comparison of the Japanese and UICC classifications and proposal for a new staging system. Union Internationale Contre le Cancer.

In the 4th edition of General Rules for the Study of Pancreatic Cancer by the Japan Pancreas Society (JPS), published in 1993 (English version published in 1996), a system resembling the TNM classification by the Union Internationale Contre le Cancer (UICC) was adopted, based on the results of precise analysis of data from 11,317 cases of carcinoma of the pancreas registered by the JPS during the 10-year period from 1981 to 1990. We compare the two TNM classifications and staging groups, focusing on the simplicity and reproducibility of the diagnostic criteria and the reliability of predicting outcome. To compare the prognostic value of the two classification systems, we analyzed the published data on resected cases registered by Pancreatic Cancer Registration Committee of the JPS. The results showed that a major drawback of the JPS classification is that is difficult to apply and has poor reproducibility. Survival rates differed significantly among the four stages in the JPS classification, whereas the UICC staging system did not reflect differences in outcome among the four stages, especially between stages II and III. The prognostic value of the UICC T category is better than that of the JPS T category, whereas the N category of JPS has better prognostic value than that of the UICC system. Believing that a combination of the two systems would solve this problem, we propose a new TNM classification and stage-grouping system that draws on the merits of both. This new system may provide improvements in staging classification that will lead to the establishment of a more practical and universal staging system for ductal carcinoma of the pancreas.

Humans↗

Effect of zinc administration on pancreatic regeneration after 80% pancreatectomy.

We studied the effect of oral zinc administration on functional and morphological regeneration of the remnant pancreas after 80% pancreatectomy in dogs. After 80% pancreatectomy, both endo- and exocrine function (assessed by the sum of plasma immunoreactive insulin on the intravenous glucose tolerance test and amylase output on the cerulein-secretin test) markedly deteriorated, the pancreatic regeneration rate (change in weight of the remnant pancreas between the time of surgery and autopsy) was very poor, and the zinc concentration in pancreatic tissue decreased in dogs fed the standard diet. In dogs fed the high-zinc diet, pancreatic function and regeneration rate were significantly improved, and the zinc concentration in pancreatic tissue was maintained. Early cell proliferation (assessed by ornithine decarboxylase activity. DNA synthesis, and proliferating cell nuclear antigen labeling index in the remnant pancreas) after pancreatectomy was significantly enhanced in the high-zinc diet group compared to the standard diet group. Correlation analyses between parameters of early cell proliferation and zinc concentration in pancreatic tissue yielded significant positive correlations, and the zinc concentration in pancreatic tissue was significantly correlated with both endo- and exocrine function and the pancreatic regeneration rate. These results suggest that a high-zinc diet after major pancreatectomy is effective in maintaining the zinc concentration in pancreatic tissue, which not only enhance early cell proliferation in the remnant pancreas but improves pancreatic endo- and exocrine function in the late period, promoting pancreatic regeneration.

Animals↗

Therapeutic effects of continuous intraarterial antibiotic infusion in preventing pancreatic infection in experimental acute necrotizing pancreatitis.

To determine the efficacy of antibiotics in the prevention of pancreatic infection and the process of aggravation after induction of acute pancreatitis, antibiotic was administrated intravenously or intraarterially, starting 6 h after acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct. Flomoxef, recognized as an antibiotic able to penetrate well into pancreas tissue, was selected for the present study. Animals were divided into three groups: no antibiotic given (Group A), antibiotic given intravenously as a bolus injection of 25 mg/kg every 6 h (Group B), and antibiotic infused continuously into the celiac trunk (4 mg/kg/h) (Group C). Compared with Group A, continuous intraarterial infusion of antibiotic (Group C) significantly improved the survival rate and decreased the serum levels of phospholipase A2(PLA2) activity and endotoxin. Furthermore, it completely prevented the occurrence of pancreatic infection, not only ameliorating the severity of pancreatic necrosis but also reducing the activity levels of amidase, trypsin-like enzyme, and PLA2 in pancreas tissue. Group B showed little beneficial effect. Antibiotic concentration in peripheral blood and pancreas tissue was significantly higher in Group C than in Group B. These results suggest that continuous arterial infusion of antibiotics into the feeding artery of the pancreas is an effective modality for preventing pancreatic infection and aggravation of severe acute pancreatitis.

Amidohydrolases↗

[The regional skin temperature of hand under different clothing conditions].

The change in the regional skin temperature of hand was investigated under two different clothing conditions. The skin temperatures at six points on the palm, dorsum, and middle finger of the hand, respectively, were measured by using thermister thermometers simultaneously. The measurements were performed in a climate chamber conditioned at 20 degrees C and 65% R.H.. The subjects were 10 healthy females aged between 20 and 24 years. Five out of the 10 subjects wore light clothing (ca. 0.36 clo) and the others heavy clothing (ca. 0.75 clo). They first rested sitting on a chair for 30 min in the climate chamber before the onset of measurement. The results are as follows: 1) The skin temperature of the palm was higher than that of the other parts. Data were rather scattered in the case of the middle finger. 2) The skin temperature of the middle finger dropped to about 3 degrees C within 20 min after the start of measurement. 3) The skin temperature of the middle finger was affected by the clothing condition. We imagine that the skin temperature of the middle finger closely relates to arteriovenous anastomoses (AVA) located in the finger. Clothing probably plays an important role in controlling the blood flow of the AVA vessels, and consequently the skin temperature of the middle finger changes more sensitively than other parts of the hand.

Adult↗

[Diagnosis and surgical treatment for endocrine tumors of the pancreas].

Clinical features, diagnostic accuracy of imaging study, and the outcome of surgical treatment for endocrine tumors of the pancreas were analyzed in 12 patients who underwent surgery for the past 16 years and 11 months. The 12 cases were classified into two groups: functioning tumors in 8 (insulinoma in 7 including one malignant case, and malignant glucagonoma in one), and nonfunctioning tumors in 4 including 3 malignant cases. In functioning tumors, tumor size was 2 cm or less in 6 benign cases, but 5 cm or more in 2 malignant cases. In nonfunctioning tumors, tumor size was larger, ranging from 3.5 to 8.0 cm. Diagnostic accuracy for localization of functioning tumors was 66.7% for US, 75.0% for CT, 66.7% for endoscopic retrograde pancreatography (ERP), and 50.0% for selective angiography, while all nonfunctioning tumors could be detected by any diagnostic imagings. Percutaneous transhepatic portal venous sampling for immunoreactive insulin was very helpful to localize insulinoma. Stenosis or obstruction of the main pancreatic duct on ERP and arterial encasement on angiography highly suggested a malignant tumor. Even for malignant cases with liver metastasis, resection of the primary tumor with debulking of metastatic disease or intraarterial infusion chemotherapy was considered to prolong patient prognosis.

Adult↗

A case of radical resection for solid cystic tumor of the pancreas with widespread metastases in the liver and greater omentum.

Solid cystic tumor (SCT) of the pancreas is known to be a low-grade malignant tumor and distant metastasis is very rare. A 50-year-old Japanese female was hospitalized because of a large mass in the upper abdomen. Computerized tomography revealed a large calcified tumor in the body-tail of the pancreas, and multiple liver tumors. Abdominal angiography demonstrated the pancreatic tumor and multiple hepatic tumors as a hypervascular mass, and disclosed a small tumor stain in the branch of the right gastroepiploic artery. The patient underwent a distal pancreatectomy with splenectomy, extended right hepatic lobectomy, and removal of the omental metastases. Histopathological and electron microscopic studies made a definitive diagnosis of SCT. She is well without any signs of tumor recurrence 1 yr and 2 months after the operation. This may be the first patient receiving simultaneous radical resection for both the main tumor and widespread distant metastases.

Cysts↗

Role of bacterial infection in diet-induced acute pancreatitis in mice.

This study was performed to elucidate the role of bacterial infection in acute pancreatitis in young female mice fed a choline-deficient diet supplemented with 0.5% DL-ethionine (CDE diet). Mice were randomly classified into two groups: one had been fed CDE diet alone (nonantibiotic group), the other was fed a CDE diet with oral administration of antibiotics (antibiotic group). Survival rates at 96 and 144 h after introduction of the CDE diet were significantly improved in the antibiotic group, 25.0 and 19.4%, respectively, as compared with 3.6 and 0% in the nonantibiotic group (p, 0.05). Aerobic and anaerobic bacterial cultures of blood, ascites, spleen, and pancreas were taken from living mice 72 h after introduction of the CDE diet. Positive bacterial growth from one or more of the specimens occurred in 29.4% of the nonantibiotic group, and in 10.0% of the antibiotic group. Mice with pancreatic necrosis had a higher positive culture rate, 62.5% in the nonantibiotic group vs 20.0% in the antibiotic group. These results suggest that reduction of intestinal flora in mice inhibits secondary infection caused by bacterial translocation and improves survival in diet-induced hemorrhagic pancreatitis. We believe the development of bacterial infection of gut origin may be a factor influencing mortality in severe pancreatitis.

Acute Disease↗