Yuro Shibayama

Endotoxin hepatotoxicity augmented by ethanol

To determine whether alcohol increases endotoxin hepatotoxicity, we administered ethanol (4.8 g/kg body wt in 4 ml of water) to rats through a gastric tube, then immediately injected endotoxin (2, 2.5, or 3 mg/kg body wt). In the rats pretreated with ethanol, the injection of 2 mg/kg body wt of endotoxin induced a slight rise of serum transaminase. However, when 2.5 mg/kg body wt of endotoxin was given, there were no significant histopathological or biochemical differences between the rats pretreated with ethanol and those pretreated with water. Moreover, there was no significant difference in mortality rates between the rats pretreated with ethanol and the controls when 3 mg/kg body wt (LD50) of endotoxin was injected. These results suggest that acute administration of alcohol enhances endotoxin hepatotoxicity when the dose of endotoxin is small, but that the effect of alcohol is masked when larger doses of endotoxin are given.

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis

BackgroundHepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors.MethodsEighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis.ResultsThe overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly.ConclusionsOptimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.

Unfavorable effect of knee immobilization on Achilles tendon healing in rabbits.

This study was undertaken to assess the effect of knee immobilization on the treatment of Achilles tendon rupture. After their Achilles tendons were severed, rabbits were divided into 2 groups. In Group A, only the ankle joint was immobilized. In Group B, both the knee and ankle joints were immobilized. At 4 weeks after surgery, both the ultimate tensile force and stiffness of the severed tendons were significantly greater in Group A than in Group B. In Group A, dense collagen fibers were seen in the repaired tendons, and the bundles of collagen fibers were parallel to one another along the axis of the tendons. In contrast, in Group B, dilated veins and capillaries were seen in the repaired tendons, and the proliferation of connective tissue containing collagen fibers was severely reduced around these veins and capillaries and was in general irregular and uneven. These results suggest that knee immobilization retards the healing of a ruptured Achilles tendon without suture, due to congestion and tension deprivation produced by keeping the tendon static.

AN AUTOPSY CASE

A diagnosis of the heritable disorder Sipples syndrome was made in a Japanese male aged 28 years. The coexistence of bilateral pheochromocytomas, bilateral medullary thyroid carcinomas and secondary hyperplasia of parathyroid was confirmed at the time of autopsy. Pancreatic islets were hyperplastic with marked proliferation of A and D cells. Transition of the ductal cell to the islet, i.e. ‘nesidioblatosis’ was observed. There was no proliferation of B cells, but a retention of B cell granules, a manifestation of suppressed secretion of insulin attributed to the overproduction of catecholamines was evident. In the stomach, numerous petechial hemorrhages and proliferation of gastrin cells were found. The pathogenesis of changes in the pancreatic islets and stomach is discussed from the viewpoint of hormonal disorders induced by pheochromocytoma and medullary thyroid carcinoma such as are found in Sipples syndrome. ACTA PATH. JAP. 27: 739˜748,1977.

Preoperative Evaluation of Local Invasion and Metastatic Lymph Nodes of Colorectal Cancer and Mesenteric Vascular Variations Using Multidetector-Row Computed Tomography Before Laparoscopic Surgery

Objective: To evaluate local invasion and lymph nodes metastasis of colorectal cancer and mesenteric vascular variations using multidetector-row computed tomography (MDCT) before laparoscopic colorectal surgery. Methods: Fifty-one patients with colorectal cancer underwent MDCT. The evaluation items were as follows: (1) local invasion; (2) detected lymph nodes evaluated by short-axis diameter, long-axis diameter, short/long axis diameter ratio, and computed tomography (CT) attenuation; and (3) visualization of mesenteric artery and vein by 3-dimensional-CT angiography. Results: First, in the evaluation of local invasion, overall accuracy was 94.1%. Second, the point of 0.8 or greater in short/long-axis diameter ratio was best index for the diagnosis of metastatic lymph nodes. Using this index, the accuracy of the diagnosis per node was 80.5%. Third, 3-dimensional-CT angiography correctly demonstrated variations of the mesenteric artery and vein. Conclusions: The MDCT was effective for evaluation of local invasion and lymph nodes metastasis of colorectal cancer and mesenteric vascular variations before laparoscopic surgery.

Prevention of hepatotoxic responses to chemicals by glycyrrhizin in rats

To clarify whether glycyrrhizin, the aqueous extract of licorice root and a drug for treatment of chronic active hepatitis, prevents the development of hepatic injury induced by carbon tetrachloride, allyl formate, and endotoxin, the present study was undertaken in rats. The treatment with glycyrrhizin 20 hr before carbon tetrachloride administration protected the development of the pericentral hepatocellular necrosis. Glycyrrhizin treatment 2 hr prior to the administration of allyl formate also inhibited the development of the periportal hepatocellular necrosis. However, glycyrrhizin did not protect the development of endotoxin-induced focal and random hepatocellular necrosis. These experimental results suggest that glycyrrhizin has no protective effect on hepatic injury following sinusoidal circulatory disturbance as seen in the case of endotoxin and that glycyrrhizin can protect against hepatotoxicity induced by the direct action on the hepatocytes due to hepatotoxins, such as carbon tetrachloride and allyl formate.

Morphogenesis of vertebral deformities in involutional osteoporosis. Age-related, three-dimensional trabecular structure.

Study Design. The relation between the semiquantitative data of alteration in three‐dimensional trabecular structure and deformities of the vertebral body was analyzed to clarify the morphogenesis of vertebral deformities in involutional osteoporosis. Objectives. To evaluate semiquantitatively the age‐related alterations of the three‐dimensional structure of trabeculae of the vertebral body and to clarify their relation to vertebral deformities in involutional osteoporosis. Summary of Background Data. Recent studies have shown that bone fractures and deformities in osteoporosis do not depend only on a reduced amount of bone tissue. There is no previous study on the relation between bone deformity and the alterations of the three‐dimensional structure of trabeculae. Methods. The second lumbar vertebrae were removed at autopsy from 25 patients who had no disease predisposing them to secondary osteoporosis and no severe vertebral deformities. The sections of the vertebral body were immersed in sodium hypochlorite solution to corrode the bone marrow. Atrophy of trabeculae and increased spacing between trabeculae were evaluated semiquantitatively under stereoscopic microscopy. The authors examined the relation between the semiquantitative data found in the autopsy vertebrae and the patterns and frequencies of each deformity of the second lumbar vertebrae in 99 patients with involutional osteoporosis. Results. The most frequent vertebral deformity was wedge‐shaped vertebrae with compression of the anterosuperior portion, and the alterations of the trabecular structure of the anterosuperior portion were severe and closely related to aging. Severe trabecular alterations with no relation to aging did not necessarily cause vertebral deformity. Conclusions. Trabecular abnormality, which is significantly correlated with aging, may be the necessary and sufficient condition for vertebral deformities in involutional osteoporosis.

SINUSOIDAL STENOSIS AS THE CAUSE OF PORTAL HYPERTENSION IN CHOLINE DEFICIENT DIET INDUCED FATTY CIRRHOSIS OF THE RAT LIVER

The anatomical lesion of the liver is evaluated as being responsible for development of portal hypertension through measurement of portal vein pressures, hemodynamical analysis of Isolated perfused livers, diameter measurement of intrahepatic vascular trees, and histological as well as his‐tometrical examinations of the liver in rats fed with choline deficient diet. The mean portal vein pressure was elevated from the normal level, 132 mm H2O to 175 mm H2O In fatty liver, to 179 mm H2O In fatty liver with fibrosis, and to 218 mm H,0 in fatty cirrhosis of liver. The hepatic blood flow of the isolated perfused rat liver definitely decreased from the normal level, 3.0 ml/g/min to 1.2 ml/g/min in fatty liver, 0.4 ml/g/min in fatty liver with fibrosis and 0.7 ml/g/min in fatty cirrhosis of liver under the condition of Ht 33.5% and perfusion pressure 135 mm H2O. There was no abnormality in the pre‐and post sinusoidal vessel, but the space of sinusoid was markedly diminished, reciprocally, to the enlargement of the hepatic cells. An intimate correlationship existed between portal hypertension and reduction of sinusoidal space. Connective tissue proliferation did not have much to do with the increase in hepatic vascular resistance. The present experiment suggested that reduction of sinusoidal space was the anatomical lesion related to development of portal hypertension in choline deficient diet induced fatty liver as well as fatty cirrhosis of the liver (sinusoidal hypertension).

Significance of chymase-dependent angiotensin II formation in the progression of human liver fibrosis

Aim:  Angiotensin II may contribute to liver fibrogenesis. In addition to angiotensin‐converting enzyme (ACE), chymase, which is expressed by mast cells, is also known to be an angiotensin II‐forming enzyme. However, it is unclear which of these two angiotensin II‐forming enzymes plays a more important role in liver cirrhosis progression. In the present study, the role of angiotensin II‐forming enzymes in the progression of liver cirrhosis was clarified.

Study of clinicopathological factors associated with the occurrence of synchronous multiple gastric carcinomas

BackgroundMultiple gastric carcinomas often arise in gastric mucosa with chronic gastritis, particularly severe intestinal metaplasia. In regard to such characteristics, several clinicopathological risk factors for multiple carcinomas have been reported, but no clinically useful criteria are available at present for assessing the onset of multiple gastric carcinomas. If the risk for multiple gastric carcinomas could be accurately assessed, efficient and accurate surveillance could be performed following minimally invasive therapies.MethodsIn the present study, we investigated clinicopathological differences between 94 cases of multiple early gastric carcinomas and 285 cases of solitary early gastric carcinoma. We tested 379 specimens of gastric carcinomas that had been surgically resected at the Department of General and Gastroenterological Surgery of Osaka Medical College, Japan, from April 1999 to December 2006.ResultsUnivariate analysis of clinicopathological factors in the present study showed that multiple gastric carcinomas were significantly correlated to old age (≥65 years), well- and moderately differentiated histological type, mucin phenotype (intestinal type), distribution of atrophic mucosa in the stomach (severe), degree of intestinal metaplasia in the surrounding mucosa (severe), and heterotopic glandular cysts. Multivariate analysis using the stepwise method identified age (≥65 years) and degree of intestinal metaplasia in the surrounding mucosa (severe) as significant independent risk factors for multiple gastric carcinomas.ConclusionWhile other studies have shown risk factors for multiple gastric carcinomas, the present study is unique in showing risk assessment criteria based on a combination of risk factors for multiple gastric carcinomas.