Completion radical surgery after cholecystectomy for accidentally undiagnosed gallbladder carcinoma

Abstract Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65–7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow-up examination. The 3-year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy. Electronic Publication     

Decrease in serum leptin by troglitazone is associated with preventing bone loss in type 2 diabetic patients

 The thiazolidinedione (TZD) class of antidiabetic drugs has been shown to inhibit the formation of bone-resorbing osteoclasts in vitro and to decrease bone resorption markers in vivo. These drugs also inhibit the expression of leptin in adipocytes. Less leptin can be associated with higher bone mass, based on analyses of mice deficient in leptin action. Effects of 1-year treatment with troglitazone, a member of the TZDs, on bone mineral density (BMD) and bone metabolism were examined in 25 Japanese type 2 diabetic patients. Glucose metabolism was improved, whereas body mass index and percent body fat did not change throughout the study. The percent change of BMD was negatively correlated with that of serum leptin, whereas it was not associated with changes of bone metabolic markers, type I collagen N-telopeptide (NTx), bone alkaline phosphatase (ALP), body mass index, or HbA1c. Serum leptin decreased in 68% of subjects (responders) after 1-month treatment and was consistently lower than the basal level throughout the treatment. Percent changes of BMD were significantly higher in the responders than in the nonresponders and in nondiabetic subjects at 6 and 12 months. NTx and bone ALP decreased at 1 month but increased thereafter in either group of patients. Thus, it is suggested that the decrease in serum leptin with no reduction in body fat mass by troglitazone is associated with preventing bone loss in type 2 diabetic patients. Hence, TZDs may have an advantage for diabetic patients who have risk factors for osteoporosis. Received: July 7, 2002 / Accepted: November 19, 2002 Offprint requests to: Y. Takeuchi     

The impairment of hepatocytes and sinusoidal endothelial cells during cold preservation in rat fatty liver induced by alcohol and the beneficial effect of hepatocyte growth factor

A fatty liver resulting from alcohol intake is often unattractive for grafting. In this study, we investigated the impairment of hepatocytes and sinusoidal endothelial cells (SECs) during cold preservation of alcohol-induced fatty liver and examined the efficacy of human recombinant hepatocyte growth factor (hrHGF). Rats were fed an alcohol diet. We performed histological examinations of the hepatocytes and observed the ultrastructural alteration of the SECs. Additionally, we measured hepatic transaminase and peroxidative lipids for hepatocellular injury and the hyaluronic acid uptake rate (HUR) to determine SEC injury. We added hrHGF to University of Wisconsin (UW) solution to assess the protective effect of the agent. Numerous fatty deposits were observed in ethanol-induced fatty livers. These grew with the duration of cold storage. Hepatic transaminases of the effluents increased during cold preservation in the livers of alcohol-treated rats. Additionally, peroxidative lipids in the effluents increased during cold preservation in the livers of alcohol-treated rats, whereas they were undetectable in non-alcohol-treated rat livers. The sinusoidal endothelium had severely deteriorated in the livers of alcohol-treated rats. Further, the HUR decreased with ethanol treatment and/or cold preservation. The addition of hrHGF suppressed the increase of hepatic transaminase in the effluent of cold-preserved alcohol-treated livers. Peroxidative lipids in the same effluents were undetectable. In fatty livers, both hepatocytes and SECs received severe damage during cold preservation. Furthermore, we demonstrated that hepatocellular injury was significantly inhibited by hrHGF.     

Effects of sesamin on aortic oxidative stress and endothelial dysfunction in deoxycorticosterone acetate-salt hypertensive rats

In the present study, we evaluated the relationship between the antihypertensive effect of sesamin, a lignan from sesame oil, and its antioxidative activity in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 5-week treatment period, systolic blood pressure was significantly elevated in normal diet-fed DOCA-salt animals compared with cases in sham-operated animals. Sesamin feeding, tempol (a superoxide dismutase mimetic) treatment or antihypertensive drugs combination (triple therapy; reserpine, hydralazine, hydrochlorothiazide) significantly suppressed the development of DOCA-salt-induced hypertension. Compared with sham-operated rats, the normal diet-fed DOCA-salt rats revealed marked increases in aortic superoxide (O(2)(-)) production. These increases in O(2)(-) production were significantly suppressed by sesamin feeding or tempol treatment, but not by triple therapy. Acetylcholine (Ach)-induced endothelium-dependent relaxation was markedly decreased in normal diet-fed DOCA-salt rats, compared with cases in sham-operated rats. Sesamin feeding and triple therapy significantly improved the DOCA-salt-induced impairment of endothelium-dependent relaxation. However, tempol treatment had no effect on the impaired vasodilator responses induced by DOCA-salt treatment. In DOCA-salt rats with or without sesamin feeding, systolic blood pressure significantly correlated with both aortic O(2)(-) production and endothelium-dependent vascular relaxation. These findings suggest that sesamin feeding inhibits the enhancement of aortic O(2)(-) production in DOCA-salt hypertensive rats, and this effect may contribute to the antihypertensive effect of sesamin. Sesamin feeding-induced improvement of endothelial dysfunction seems to result from the above antioxidative and antihypertensive effects.     

Modulation of 8-OH-DPAT-induced hypothermia by imipramine in rats

The effects of imipramine on 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the 5-hydroxytryptamine (5-HT)(1A)-receptor full agonist, -induced hypothermia was examined in rats. Single administration of imipramine (30 mg/kg, i.p.) attenuated 8-OH-DPAT-induced hypothermia. This effect of imipramine was blocked by the 5-HT(2A)-receptor antagonist ketanserin. 8-OH-DPAT-induced hypothermia was not altered 24 h after repeated administration of imipramine (1 - 10 mg/kg per day) for 14 days. However, 8-OH-DPAT-induced hypothermia was significantly enhanced in repeated imipramine (10 mg/kg per day)-treated rats that received 8-OH-DPAT plus imipramine 24 h after the final imipramine administration for 14 days. The 5-HT(2A)-receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)-DOI) attenuated the 8-OH-DPAT-induced hypothermia in drug naive rats. The inhibitory effect of (+/-)-DOI (0.3 mg/kg, s.c.) on 8-OH-DPAT-induced hypothermia was attenuated by repeated administration of imipramine (10 mg/kg per day) for 14 days. These findings suggest that enhancement of the 5-HT(1A) receptors by repeated administration of imipramine may be due to reduction of the inhibitory effects from the 5-HT(2A) receptors to the 5-HT(1A) receptors.     

Involvement of Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) and Rac1 in the phagocytosis of amyloid-beta(1-42) in rat microglia

Alzheimer's disease (AD) is characterized by the accumulation of extracellular amyloid-beta (A beta) fibrils with microglia. Recently, there has been great interest in the microglial phagocytosis of A beta, because the microglial pathway is considered to be one of the A beta clearance pathways in the brain parenchyma. However, the mechanism of microglial phagocytosis of A beta is not fully understood and, thus, was investigated in this study. At one minute after exposure to A beta(1-42) (A beta 42), A beta immunoreactivity was detected at the cell surface of microglia. After 1 h, marked immunoreactivity was observed in the cytosolic vesicles. At 12 h, delayed phagocytosis of fibrillar A beta 42 was also observed with the formation of a large phagocytic cup. The microglial cell shape rapidly changed to an ameboid form during the process of phagocytosis. Although neither neural Wiskott-Aldrich syndrome protein (N-WASP) nor WASP interacting SH3 protein (WISH) immunoreactivity was co-localized with filamentous actin (F-actin) distribution, both WASP family verprolin-homologous protein (WAVE) and Rac1 immunoreactivity was co-localized with F-actin in the lamellipodia of phogocytic microglia. These results suggest that WAVE and Rac1 participate in the phagocytosis of A beta 42 by microglia.     

Possible involvement of small oligomers of amyloid-beta peptides in 15-deoxy-delta 12,14 prostaglandin J2-sensitive microglial activation

In Alzheimer's disease, fibrillar amyloid-beta (Abeta) peptides form senile plaques associated with microglia. However, the relationship between Abeta peptides and microglia is not fully understood. In this study, the incubation of Abeta1-40 (Abeta40) produced small oligomers, while incubation with Abeta1-42 (Abeta42) caused large molecular aggregates. Microglial production of nitrite, interleukin-6 and tumor necrosis factor-alpha was induced by Abeta40, but not Abeta42. This production was significantly reduced by 15-deoxy-Delta(12,14) prostaglandin J(2), and it was completely suppressed by beta-sheet breaker peptide, Leu-Pro-Phe-Phe-Asp. These results suggest that small oligomers, rather than large molecular aggregates, mediate microglial activation induced by Abeta peptides.     

Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease

PURPOSE: To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS: Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical analysis of lacrimal gland biopsy specimens obtained from nine patients with cGVHD and five with Sj?gren's syndrome (SS). The regions of interest were further assessed by transmission electron microscopy. RESULTS: CD4(+) and CD8(+) T cells were mainly detected in the periductal areas of the glands of patients with cGVHD, but were distributed throughout the acinar areas in patients with SS. In the periductal areas of patients with cGVHD, a subpopulation of CD4(+) and CD8(+) T cells expressed the activation marker CD154. In addition, CD4(+) and CD8(+) T cells were colocalized with mononuclear infiltrates and stromal fibroblasts expressing the full component of surface molecules necessary for antigen presentation, including HLA-DR, CD54, CD40, CD80, and CD86. Electron microscopy revealed activated fibroblasts that embraced lymphocytes and macrophages with their processes. Also, there were more CD8(+) T cells in the glandular epithelia of patients with cGVHD than in those with SS. Intraepithelial T cells were attached to epithelial cells by several primitive contacts and colocalized with dead cells. CONCLUSIONS: The results strongly suggest that CD4(+) and CD8(+) T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.     

Laterality of the performance of glaucoma mass screening using frequency-doubling technology

PURPOSE: This study investigated laterality during the performance of glaucoma mass screening with a frequency-doubling technology perimetry test. MATERIALS AND METHODS: A frequency-doubling technology screening mode (C-20-1, version 2.6) test was performed on both eyes of 14,784 persons. Subjects with visual field abnormalities detected by the frequency-doubling technology test or with fixation error underwent retesting without a specified interval for rest. Consequently, 206 subjects who fulfilled the screening criteria of the frequency-doubling technology-based glaucoma screening protocol [FDT-GSP(+)] were further investigated using the Humphrey visual field analyzer (30-2). As a result, 74 right eyes and 57 left eyes were shown to have definite glaucoma. RESULTS: Frequency-doubling technology data for the left eye demonstrated a significantly (P<0.001) higher rate of artifacts, such as no reproducibility of results between the first and second tests (left/right: 2.4%/1.7%) as well as fixation errors (left/right: 2.8%/1.0%). The false-positive rate of the FDT-GSP for glaucoma was more than 1.5-fold higher in the left eye than in the right eye (16.3%/9.8%). In the case that either eye exhibited FDT-GSP(+), the positive predictive value of the FDT-GSP for definite glaucoma in the left eye was almost half of that in the right eye (28.4% vs. 53.8%). Specificity of the FDT-GSP for detection of definite glaucoma also exhibited a lower trend (P = 0.097) in the left eye (44.6%) than in the right eye (55.3%), but the sensitivity of the test was similar in both eyes (91.2% vs. 90.5%, respectively). CONCLUSIONS: When frequency-doubling technology-based mass screening is performed on the general population, performance is lower for the left eye than for the right eye. This performance disparity is likely to be primarily associated with a difference in specificity.