LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Histological study of effect of bone morphogenetic protein derived from bovine tooth on periosteum in rats

Summary In this study, we examined histologically the effect of a bone morphogenetic protein (BMP) derived from bovine tooth on the periosteum. Supraperiosteal injection of crude BMP into femurs of Wistar rats (28 day old) resulted in periosteal cell proliferation with subsequent bone and cartilage formation. Moreover, proliferating periosteal cells migrated into injected BMP, and formed both cartilage and bone. These observations show that exogenous BMP stimulates mesenchymal cells of the periosteum to proliferate and differentiate into osteoblasts, and therefore BMP may be one of factors which are involved in differentiation of osteoblasts in the periosteum.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

New hepatic vein reconstruction in left liver graft.

The incidence of hepatic venous stenosis is higher in partial liver transplantation. New methods for hepatic venous reconstruction in left liver transplantation, which secure wide anastomosis, were devised and are reported here. In the graft, the right side of the middle hepatic vein or the left side of the left hepatic vein was cut longitudinally and a rectangular-shaped vein patch was attached for venoplasty. In the recipient, after the left and middle hepatic veins were joined, the right side of the middle hepatic vein was cut toward the closed right hepatic vein, making a horizontal cavotomy for anastomosis. Of 92 patients who underwent conventional hepatic vein reconstruction, 3 were complicated by hepatic venous stenosis (median follow-up 43 months). By contrast, there were no hepatic vein complications in the 20 patients who underwent the new technique (7 months). The current method appears to be technically feasible for outflow reconstruction in left liver graft transplantation.     

A case of chronic hepatitis C virus-related advanced hepatocelluar carcinoma surviving more than 8 years]

A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis.     

New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma

Ultrasound (US) contrast agents such as Levovist and Sonazoid are now commercially available in Japan. Innovative contrast agents and ultrasound technologies have dramatically changed both diagnostic and treatment strategies for hepatocellular carcinoma (HCC). Contrast-enhanced US is extremely useful in the differential diagnosis of hepatic tumors as well as in evaluation of post-treatment response of HCC after lipiodol transarterial chemoembolization and radio frequency ablation. Harmonic US sensitively detects residual cancer cells in HCC patients after treatment, to facilitate accurate guidance for needle insertion for US monitoring; no other imaging modalities, including computed tomography (CT) or magnetic resonance imaging (MRI), have such capability. In 2005, the breakthrough technology of pure arterial phase imaging, which depicts only intranodular arterial accumulated maximum intensity projection images, was developed from advanced raw data storing and accumulation technologies. This technique can clearly identify whether blood supplyin the tumor is of arterial or portal origin, to facilitate the non-invasive characterization of nodular lesions associated with liver cirrhosis. Again, CT or MRI do not have such capabilities. This innovative technique can help differentiate premalignant lesions from overt HCC. Concurrent real-time imaging of multi-detector CT and US, known as real-time virtual sonography, has recently become available. This technique greatly facilitates the treatment guidance for HCC. These newly introduced sonographic techniques are dramatically changing the diagnostic and therapeutic strategies for HCC, which are expected to improve the prognosis of HCC patients.     

Neuropsychological test for the detection of dementia in elderly individuals: the Nishimura Dementia Test

Background: Progression of the core and accessory symptoms of dementia can be slowed if drug therapies and psychosocial interventions are administered at an early stage. The aim of this study was to develop and standardize a neuropsychological test for the elderly that can detect dementia at an early stage with high sensitivity and can evaluate a wide range of severities of dementia based on assessments of various cognitive functions. Methods: A preliminary test consisting of 23 items and the Nishimura Mental State Scale for the Elderly (NM Scale), which evaluates the mental functions of elderly individuals by observing their actual behaviors in daily life, were administered to 448 elderly subjects. After applying Hayashi’s quantification theory type I to the results, we revised the preliminary test to construct a neuropsychological test for the elderly, which we named the Nishimura Dementia Test (ND Test), and standardized it. Then, we examined its validity and test–retest reliability. Results: Among the 448 subjects, there was a strong correlation between the ND Test scores and NM Scale scores. The ND Test showed a good general agreement rate for the discrimination of the severity of dementia, and good sensitivity and specificity of discrimination of dementia when compared with the actual NM Scale. Using different groups of elderly subjects, the ND Test showed validity and test–retest reliability, and the ND Test scores showed strong correlations with the Revised Hasegawa Dementia Scale scores and the Mini‐Mental State Examination scores. Conclusions: The ND Test is based on assessment of a variety of cognitive functions and can evaluate a wide range of severities of dementia with good validity and reliability.