DF3 expression in human gallbladder carcinoma: significance for lymphatic invasion.

DF3 (MUC 1) is a member of a family of high molecular weight glycoproteins. Recent studies have demonstrated that DF3 is expressed in tumors of various human organs, and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. However, expression patterns of DF3 have not yet been established in human gallbladder carcinomas. In this study, we examined DF3 expression in human gallbladder adenocarcinoma and its clinicopathological significance. DF3 immunoreactivity was detected not only in the cancer cells (cytoplasmic type; 50.0%, 27/54) but also in the cancer stroma (stromal type; 46.3%, 25/54). According to TNM classification, 65.0% (26/40) of T2-4 gallbladder cancers showed cytoplasmic DF3, while 7.1% (1/14) of the T1 cancers were cytoplasmic DF3-positive (p<0.001). Stromal DF3 expression was detected in 62.5% (25/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.001). Lymph node metastasis was frequently found in the cytoplasmic DF3- and stromal DF3-positive gallbladder cancers (59.3% and 60.0%, respectively). These observations suggested that DF3 expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

CEA immunohistochemical localization is correlated with growth and metastasis of human gallbladder carcinoma.

Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e., modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human gallbladder carcinomas. In this study, we examined CEA expression in human gallbladder adenocarcinomas and its clinicopathological significance. CEA immunoreactivity was detected not only in the cancer cells (cytoplasmic type: 63.0%, 34/54) but also in the cancer stroma (stromal type: 29.6%, 16/54). According to TNM classification, 75.0% (30/40) of T2-4 gallbladder cancers showed cytoplasmic CEA, while 28.6% (4/14) of the T1 cancers were cytoplasmic CEA-positive (p<0.05). Stromal CEA expression was detected in 40.0% (16/40) and none (0/14) of the T2-4 and T1 cancers, respectively (p<0.05). Lymph node metastasis was frequently found in the cytoplasmic CEA- and stromal CEA-positive gallbladder cancers (44.1% and 62.5%, respectively). These observations suggested that CEA expression plays important roles in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Stromal expression of thrombospondin-1 is correlated with growth and metastasis of human gallbladder carcinoma.

Thrombospondin-1 (TSP1) is one of the extracellular matrix glycoproteins that affect cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we examined TSP1 expression in human gallbladder adenocarcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 74.5% (29/39) of the T2 and T3 gallbladder cancers were TSP1-positive, while none (0/14) of the T1 cancers showed TSP1 expression (p<0.001). Lymph node metastasis and venous involvement were frequently found in the TSP1-positive cases (90.0% and 87.1%, respectively) of gallbladder adenocarcinoma (p<0.001). These observations suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human gallbladder adenocarcinomas, and that stromal TSP1 immunoreactivity is a good predictor of vascular involvement and lymph node metastasis.

Micronucleus test using cultured new born rat astrocytes.

Micronuclei is induced in cytoplasm as a consequence of the formation of chromosomal fragments or remaining chromosomes during cell division by the cause of clastogens or spindle poisons, and is used as an indicator of genotoxicity screening tests. There are few short-term genotoxicity screening tests using brain cells. We attempted to establish a new in vitro micronucleus test (MN test) system by use of central nervous system cells. Primary cultured astrocytes were prepared from newborn male Sprague-Dawley (SD) rats. In growth curve of astrocytes, doubling time was determined to be 31 h. In time study, the highest frequency of micronuclei was observed at 48 h, 72 h and 6 h-exposure-66 h-recovery by vincristine (VCR), mitomycin C (MMC) without metabolic activation system and cyclophosphamide (CPM) with metabolic activation system, respectively. Dose-response relationships between micronucleus frequency and concentrations of MMC, VCR and CPM were observed, respectively. It is suggested that the in vitro MN test using new born rat-astrocytes could be used as a screening test of environmental and occupational genotoxic chemicals in the central nervous system cells.

A case report: tumorectomy for brain metastasis of hepatocellular carcinoma.

Described here is a rare case of an operation for brain metastasis of hepatocellular carcinoma (HCC) after hepatectomy. We admitted a 45-year-old male patient complaining chiefly of a visual field disturbance and headaches. He had undergone a hepatectomy due to HCC one year prior to hospitalization. He was diagnosed with a brain metastasis with intratumoral hemorrhage. He underwent a tumorectomy and hemorrhage excision. After the surgery, his neurological symptoms improved, and he was temporarily rehabilitated. The decision to operate in this case could be questionable because the patient already had a pulmonary metastasis. Nevertheless, we concluded that local therapy for such a brain metastatic lesion would be effective in alleviating his discomforts and improving his quality of life as long as the primary lesion was under control.

Acute emphysematous cholecystitis associated with pneumobilia: a case report.

This report describes a rare case of acute emphysematous cholecystitis with pneumobilia in the common bile duct. The patient was a 66-year-old woman with a part history of diabetes mellitus, and operations for gastric and breast carcinoma. The chief complaint was pain in the right hypochondrium with severe right hypochondrial tenderness and distention of the gallbladder detected on examination. Laboratory tests showed leukocytosis, marked elevation of CRP, jaundice, liver dysfunction, and hyperglycemia. Gas was detected in the gallbladder on plain abdominal X-rays and CT scans of the abdomen, and a small amount of gas was also observed in the common bile duct. On the day of admission, percutaneous transhepatic gallbladder drainage (PTGBD) was carried out under ultrasound guidance, and Clostridium perfingens and E. coli were detected in the bile. Imaging after PTGBD showed no cystic duct obstruction. On the 12th day after PTGBD, cholecystectomy and choledochotomy with primary closure were performed. The postoperative course was good and the patient was discharged on the 15th day after surgery.

Hepatic cytokeratin changes in obstructive jaundice: before and after biliary drainage.

We investigated the changes in hepatic cytokeratins in obstructive jaundice by immunohistochemistry. The results can be summarized as follows: 1) In accordance with the progression of the jaundice, the lobular and cellular distribution of cytokeratin reactivity in hepatocytes expanded. 2) Cytokeratin reactivity in obstructive jaundice was improved by removal of the bile duct obstruction (decompression), but this decompressive effect deteriorated in the case of prolonged jaundice. 3) It is suggested that the specific lobular and cellular distribution and/or the changes in cytokeratin aggregation might be of value in determining the stage and in predicting the prognosis of obstructive jaundice.

[Extracorporeal shock wave lithotripsy for choledocholithiasis].

By the advent of extracorporeal shock wave lithotripsy (ESWL), the plan to manage choledocholithiasis has changed greatly. As a non-operative treatment, endoscopic sphincterotomy (EST) is intensively performed, but ESWL is much safer than EST in invasiveness and complications. Without EST, 5 Fr endoscopic naso-biliary drainage (ENBD) and percutaneous transhepatic biliary drainage (PTBD) aiming at preservation of the function of the papilla Vater were inserted to make drainage first for the patients with choledocholithiasis with obstructive jaundice who visited our hospital. After the cholangitis subsided, ESWL was performed under the direct cholangiography through ENBD and PTBD and excellent results were obtained which are herein reported. ENBD has been performed on 98 cases of choledocholithiasis over the past 4 years. ESWL has been performed on 42 cases (ENBD 36 cases and PTBD 6 cases). Choledocholithiasis completely disappeared in 31 cases (73.8%). For unsuccessful cases, EST, percutaneous transhepatic cholangioscopy (PTCS), or laparotomy was performed.

[Clinical evaluation of operative and non-operative treatment in hepatocellular carcinoma with main portal vein tumor thrombus].

It has been well recognized that results of treatment in hepatocellular carcinoma with main portal vein tumor thrombus (Vp 3 HCC) are very poor. But we tried aggressive transcatheter treatment (one shot or continuous hepatic arterial infusion, TAE) and hepatectomy with postoperative TAE in 52 cases by Vp3 HCC in recent 10 years. Analysis of the results disclosed that PR or CR cases were observed only in the series of continuous hepatic arterial infusion therapy. And cumulative survival rate was the best in the series of hepatectomy (50% survival interval is 18 months). We concluded that hepatectomy and resection of the tumor thrombus with postoperative TAE is the best treatment in Vp3 HCC.

[Hepatic arterial infusion chemotherapy using implantable reservoir in colorectal liver metastasis].

Hepatic arterial infusion chemotherapy was performed in 47 cases with colorectal liver metastasis. Methods of hepatic arterial cannulation were as follows: operative insertion of polyvinyl chloride catheter in 12 cases, angiographic insertion of polyethylene catheter via the left high brachial artery in 20 cases and operative implantation of reservoir in 15 cases. Mean durations of chemotherapy were 31 days, 25 days and 115 days, respectively. Chemotherapies were discontinued because of complications and catheter troubles in 7 cases (58%), 8 cases (40%) and 6 cases (40%), respectively. Regression of tumor size was observed only in the group with reservoir. Prolonged therapy is achievable by use of the reservoir. But catheter troubles, including obstruction, infection, extravasation and pseudoaneurysm, are still observed in the course of chemotherapy. Radionuclide study using 99m Tc macroaggregated albumin is useful to detect catheter troubles. We stressed that the proper management of reservoirs is important.

[Basic studies on oral administration of lentinan (I)--influence on lymphocyte subsets in peripheral venous blood].

The effect of oral administration of lentinan (LTN), a biological response modifier, in the control of systemic immune function was studied in 6-week old male Wistar-Imamichi SPF rats. In the LTN group, 1 mg LTN dissolved in 1 ml physiological saline was administration forcibly into the stomach twice weekly. Physiological saline alone was administered in a similar fashion to the control group. Blood samples were obtained prior to and after four and eight weeks of administration. White blood cells and lymphocyte counts were obtained and lymphocyte subsets were measured using monoclonal antibodies W3/13, W3/25 and 0 X 8 (Sera-Lab), and a laser flow cytometry system (Orthospectrum III, Orthodiagnostic System). The T cell ratio, helper/inducer T (Th) cell ratio, and suppressor/cytotoxic T (Ts) cell ratio were measured. The peripheral white blood cell count and lymphocyte count were not significantly different between the control and LTN groups. After four weeks of LTN administration, however, the LTN group showed a significantly higher T cell ratio, Th cell ratio and Th/Ts cell ratio than did the control group, and the Ts cell ratio was significantly lower. In the groups undergoing administration for eight weeks, no difference was noted in the lymphocyte subsets between the two groups. Oral administration of LTN apparently modulates the systemic immune function through T cell stimulation, especially Th cells, but continued administration may induce a tolerance to the effect of LTN.

Hemolytic streptococcus preparation OK-432; beneficial adjuvant therapy in recurrent gastric carcinoma.

The administration of a hemolytic streptococcus preparation, OK-432, is thought to be of therapeutic value in the treatment of cancer patients through a stimulatory effect on the immune system. In order to evaluate any beneficial effect of such an administration, a group of patients with recurrent gastric cancer was studied. This group was randomly subdivided into 3 groups: 1) Intradermal group (ID Group), 42 patients given an intradermal injections of OK-432. 2) Intramuscular group (IM Group), 40 patients given an intramuscular injections of OK-432. 3) Control group (C Group), 39 patients not given injections. Each group was studied in regards to the length of survival, the host immune response and the incidence of side effects. When compared to the IM and C Groups, the ID Group showed improved survival. Accompanying this improved survival, the ID Group also had greater white cell and lymphocyte counts, a greater number of T cells, and a more dramatic skin reaction to the extracted cell wall polysaccharide of hemolytic streptococcus Su-strain (Su-PS). The ID Group, following OK-432 injection, had a 4.8% incidence of fever and a 52.4% incidence of local abscess formation at the injection site. 90% of the IM Group developed fever but abscess formation was absent in all patients. From these results, it was concluded that in the patients tested, intradermal injection of OK-432 appears to be clinically superior to intramuscular injection.

Effects of oral administration of streptococcal preparation OK-432 on thoracic duct lymphocytes.

One KE of streptococcal preparation OK-432 (PIC) was given orally to 6-week old male Wistar-Imamichi rats twice weekly, and control animals received comparable volumes of saline alone. Samples of thoracic duct lymph and posterior vena caval blood were collected prior to and 4 and 8 weeks following PIC. The T cell count of thoracic duct lymphocytes was about three times greater than that of venous blood specimens, and increased significantly in animals following PIC. Controls showed only a slight increase followed by a decrease, so that by 8 weeks of treatment with PIC, the thoracic duct T cell count revealed a significantly greater number in the PIC group than in the controls. In addition, after 8 weeks the per cent T cell subpopulation in thoracic duct lymph increased significantly in the treated group, but it declined in the control group. Concerning T cell subsets in thoracic duct lymphocytes, the percentage of suppressor/cytotoxic T cells showed a significant elevation in the control group after 4 weeks compared with the treated group. No other blood or lymph variables reached statistical significance in this respect.

Protective effect of inactivated virus vaccine on Sendai virus infection in rats.

Rats which had received two doses of inactivated Sendai virus vaccine were resistant to intranasal virus challenge. Vaccination was equally effective when administered by intravenous, intraperitoneal, intramuscular, or subcutaneous routes but not the intranasal route. Rats vaccinated intraperitoneally with inactivated Sendai virus vaccine were protected from contact infection. Suckling rats born to vaccinated dams were resistant to challenge infection at 3 weeks of age, but the resistance was not demonstrated after weaning at 4 weeks of age.

[Antibody production in rats vaccinated with inactivated Sendai virus (author's transl)].

Adult male and female rats were inoculated with tween 80-ethylether-formalin-ultraviolet inactivated Sendai virus (Sv-V) and examined for the production of hemagglutination inhibition (HI) antibody. There were no significant differences in the antibody titers between males and females, and among the various routes of inoculation except for the intranasal which was not effective. The antibody became detectable 7 days after a single inoculation with 10(5) HAU of Sv-V. The antibody titer, which had its peak 21 days after the inoculation, persisted for 200 days and declined gradually thereafter. The HI antibody titers were correlated with inoculated Sv-V doses and a predominant booster reaction with the vaccine was observed. Maternal antibodies were detected in sucklings born to dams hyperimmunized with the vaccine. The titers were similar to those of the dams until 3 weeks after birth but declined rapidly after weaning at 4-week-old. The titers of fetuses and neonates before suckling were significantly lower than those of the sucklings.