Pathomorphological description of the shunted portion of a filum terminale arteriovenous fistula

Background contextThe clinical morphology of a filum terminale arteriovenous fistula (f-AVF) is well known; however, pathological details of the fistulized portion are unknown. Herein, we report the pathological findings of the f-AVF.Study designCase report and literature review.PurposeTo present a detailed pathological examination of the fistulized portion of the f-AVF.MethodsA 71-year-old man presented with gradually worsening bilateral foot paresthesias and anal dysesthesia. T2-weighted magnetic resonance imaging showed flow voids surrounding an edematous conus medullaris and cauda equina with spinal stenosis at L3–L4 and L4–L5. Spinal digital subtraction angiography demonstrated an f-AVF fed by the left T9 intercostal artery.ResultsWe performed laminotomies of L3 and L4 to open the dura mater and found a hypertrophic filum terminale. It was resected, leaving a length of 2 cm between the abnormal proximal end and normal distal end. The f-AVF completely disappeared after the surgery. On pathological examination, the filum terminale included two vessels at the proximal end and one at the distal end. At the proximal end, immunostaining showed one vessel that was definitively an artery with both an internal elastic membrane (IEM) and smooth muscle. The other was a vein and lacked an IEM. On the distal side, the collagen fibers gradually increased, the IEM partially disappeared from the arterial wall, and the vein became arterialized with a thin IEM. At the distal end the two vessels joined. Therefore, we speculated that the fistulized portion of the f-AVF was not a fistula point but had some lengths where the artery had characteristics of a vein and there was venous arterialization.ConclusionsThe filum arteriovenous shunting occurred at the portion where there was venous arterialization and the artery had the characteristics of a vein. Therefore, resecting the filum terminale requires more proximal from the normal distal end.     

Prediction of incontinence following low anterior resection for rectal carcinoma

PURPOSE: This study was performed to predict incontinence following low anterior resection for rectal cancer. METHODS: Preoperatively, 21 patients were evaluated via patient history and a physical examination that included anal manometric studies. Six months postoperatively, repeat manometric studies and clinical evaluations were performed to assess the level of continence. Degree of continence was graded based on severity of the dysfunction and grade of the continence score. RESULTS: The formula used for predicted postoperative resting pressure is as follows: predicted postoperative resting pressure=0.42 × preoperative resting pressure+1.56 × length of remaining rectum+12.37 (R ² =0.58;P <0.001). It was demonstrated that patients with low predicted postoperative resting pressures (<30 mmHg) had incontinence, and those with high predicted postoperative resting pressures (>35 mmHg) were continent. There were significant correlations between length of the remaining rectum and ratio of the decrease in maximum resting pressure (postoperative/preoperative maximum resting pressure;r =0.63;P <0.01). CONCLUSIONS: Continence following low anterior resection may be influenced by maximum resting pressure function of the internal anal sphincter; if it is injured during surgery, incontinence will occur. We may be able to foretell incontinence by using the predicted postoperative resting pressure formula, which is calculated by using preoperative resting pressure measurements and then determining the length of the remaining rectum.Abstract presented at the meeting of The Japanese Society of Gastroenterological Surgery, Tokyo, Japan, July 18 to 19, 1996.     

Endoscopic diagnosis of pancreatic cancer using intraductal ultrasonography

BACKGROUND/AIMS: At present developed modalities are not sufficient for detecting early stage pancreatic cancer. We previously reported the clinical usefulness of intraductal ultrasonography in various pancreatobiliary diseases. In the present study we assessed the usefulness of intraductal ultrasonography in diagnosing pancreatic cancer. METHODOLOGY: Thirty-one patients with pancreatic cancer were examined by intraductal ultrasonography. We approached the main pancreatic duct (pancreatic duct-intraductal ultrasonography) in 24 of 31 patients and the bile duct (bile duct-intraductal ultrasonography) in 20 patients with pancreatic cancer. We compared the diagnostic ability of pancreatic duct-intraductal ultrasonography with that of extracorporeal ultrasonography, computed tomography, endoscopic ultrasonography or endoscopic retrograde pancreatography. We examined the usefulness of bile duct-intraductal ultrasonography in diagnosing tumor invasion to the bile duct. RESULTS: Pancreatic duct-intraductal ultrasonography was able to demonstrate a tumor in 22 of 24 patients. Extracorporeal ultrasonography, computed tomography, endoscopic ultrasonography or endoscopic retrograde pancreatography detected tumors in 26, 27, 29, 29 of 31 patients, respectively. In two patients, only intraductal ultrasonography could demonstrate a tumor, which was not detected by any other modalities. We examined bile duct invasion of the tumor according to our grading system. The overall accuracy rate was 90%. No complications were noted in any patients throughout the study period. CONCLUSIONS: Intraductal ultrasonography is useful to diagnose pancreatic cancer, and it is suggested that it should be actively performed after endoscopic retrograde pancreatography.     

Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice

Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) have been implicated in atherogenesis. However, the precise role of TNF-alpha in atherogenesis is still unclear. To examine the effect of TNF-alpha on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-alpha (apoE-/-/TNF-alpha-/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF-alpha-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-alpha-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-alpha-/- mice (n=8, 3.1+/-0.4%) was significantly smaller than that of apoE-/- mice (n=7, 4.7+/-0.4%, p<0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-alpha-/- mice (n=10, 5.1+/-0.3 x 10(5)microm(2)) was also significantly smaller than that of apoE-/- mice (n=11, 7.0+/-0.3 x 10(5)microm(2), p<0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF-alpha-/- mice. Macrophages from apoE(-/-) mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF-alpha-/- mice. These results indicate that TNF-alpha plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.     

Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo

The present study was designed to evaluate the therapeutic efficacy of adenovirus-mediated wild-type (wt) tumor suppressor p53 expression in four human thyroid carcinoma cell lines harboring p53 mutations (ARO, FRO, NPA, and WRO) and normal human thyroid follicular cells with wt-p53 in vitro and in vivo. In vitro infection of replication-deficient recombinant adenovirus vector expressing wt-p53 led to a dose-dependent cell killing in both normal and carcinoma cells. In contrast, adenovirus expressing Escherichia coli beta-galactosidase showed little effect. The sensitivity to p53-mediated cell killing varied among the cells used. It was, at least partly, dependent on their adenovirus infectivity in carcinoma cells, whereas normal thyroid cells were relatively resistant to p53-mediated cell death despite its highest adenovirus infectivity. The mechanism of cell killing by wt-p53 was shown, by flow cytometric analysis, to be apoptosis. Furthermore, wt-p53 expression renders two out of four carcinoma cell lines (FRO and NPA) more sensitive to doxorubicin and one (FRO) to 5-fluorouracil, independent of treatment schedule. In vivo experiments, using FRO and NPA cells, showed that growth of sc tumors in nude mice was nearly completely inhibited by direct injection of adenovirus expressing wt-p53 [1 x 10(9) plaque-forming units/tumor]. This effect was augmented by its combination with doxorubicin treatment (4 mg/kg, thrice a week), which led to tumor regression. Our results therefore indicate that adenovirus-mediated wt-p53 gene introduction seems to be a potential clinical utility in gene therapy for anaplastic thyroid carcinomas, particularly when combined with chemotherapy.     

Involvement of stress-activated protein kinase/c-Jun N-terminal kinase in endothelin-1-induced heat shock protein 27 in osteoblasts

OBJECTIVE: We have reported that endothelin-1 (ET-1) activates p38 mitogen-activated protein (MAP) kinase through protein kinase C in osteoblast-like MC3T3-E1 cells, and that p38 MAP kinase plays a role in the ET-1-induced heat shock protein 27 (HSP27). Recently, we found that stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by ET-1 in these cells. In the present study, we have investigated the involvement of SAPK/JNK in ET-1-induced HSP27 in MC3T3-E1 cells. METHODS: The concentration of HSP27 in soluble extracts of the cells, the expression of mRNA for HSP27, and the phosphorylation of SAPK/JNK were determined by an enzyme immunoassay, Northern blot analysis, and Western blot analysis respectively. RESULTS: SP600125, a specific inhibitor of SAPK/JNK, markedly reduced ET-1-stimulated HSP27 accumulation. The inhibitory effect of SP600125 was dose dependent in the range between 1 and 50 microM. SP600125 reduced the ET-1-increased level of HSP27 mRNA. Calphostin C and Go 6976, inhibitors of protein kinase C, reduced the ET-1-induced phosphorylation of SAPK/JNK. 12-O-Tetradecanoylphorbol-13-acetate, a direct activator of protein kinase C, induced SAPK/JNK phosphorylation, which was suppressed by SP600125. A combination of SP600125 and p38 MAP kinase inhibitor such as SB203580 and PD169316 additively reduced the ET-1-stimulated accumulation of HSP27. CONCLUSIONS: These results strongly suggest that JNK plays a part in ET-1-induced HSP27 in addition to p38 MAP kinase in osteoblasts.