Fasciitis-panniculitis syndrome and advanced gastric adenocarcinoma in association with antibodies to single-stranded DNA.
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Publications and source records attributed to T Sawai.
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BACKGROUND: Hepatic blood flow was associated with degree of hepatic damage. Measurements of blood flow using ultrasonography (US) may vary due to any observer's and patient's conditions. The utility of magnetic resonance imaging (MRI) flowmetry in portal and hepatic veins was assessed. PATIENTS AND METHODS: Using the phase-contrast method, the mean flow velocity of portal (PVF) and hepatic vein (HVF) were determined by MRI and US in 75 consecutive patients with liver diseases, including 58 patients undergoing hepatectomy. The correlations between these parameters and clinicopathological findings were examined. RESULTS: PVF and HVF measured by MRI flowmetry were 12.8+/-4.5 and 14.7+/-5.3 cm/s, respectively. There was no significant correlation of both flows between MRI and US. PVF correlated significantly with portal pressure (r = -0.722; P < 0.05). There was a negative correlation between HVF and histological activity index score (r = -0.366; P < 0.05). PVF and HVF were lower in patients with cirrhosis and higher staging score (2-4) and PVF was lower in patients with higher grading score (2-3; P < 0.05). PVF and HVF were not significantly associated with postoperative complications. CONCLUSIONS: Our results suggest that MRI flowmetry is a potentially useful tool for measurement of hepatic blood flow and recommend its use for estimation of liver cirrhosis-associated impairment.
OBJECTIVE: Apoptosis of chondrocytes plays a pivotal role in cartilage degeneration. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and has been assumed to cause the degradation of human cartilage. To investigate the mechanisms of TNF-alpha-mediated apoptosis of human chondrocytes from a point of view of the balance between the caspase-cascade and the expression of inhibitor of apoptosis proteins (IAPs), although both of them are induced with TNF-signals. METHODS: The expression of TNF-receptors (TNF-Rs) in normal human articular chondrocyte (NHAC-kn) was examined with immunocytochemistry. Subconfluent cultures of NHAC-kn were tested with TNF-alpha and/or actinomycin D (actD), and the induction of apoptosis was evaluated by the frequency of apoptotic cells visualized with nuclear staining using Hoechst 33342. The activation of caspases and the expression of IAPs were examined with Western blot analyses. RESULTS: NHAC-kn expressed TNF-R1 and -R2. When NHAC-kn was treated with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml) for 24 h, the frequency of apoptotic cells increased to more than 25%. TNF-alpha alone, however, induced the apoptosis insufficiently (up to 8.3%), even when used at the concentration of 100 ng/ml for 48 h. In apoptotic human chondrocytes induced with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml), the caspase-3, -8, and -9 were activated and the protein expression of XIAP and c-IAP1 decreased. CONCLUSIONS: In apoptotic human chondrocytes induced with TNF-alpha and actD, the balance between caspase activation and IAPs' expression lay with the executioner caspase (caspase-3) and led to decreased expression of XIAP and c-IAP1.
AIMS: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that undergoes increased expression in colorectal carcinomas, but its prognostic value is a topic of debate. The aim of this study is to clarify the prognostic value of PD-ECGF expression in colorectal carcinomas. METHODS: PD-ECGF expression was measured by enzyme-linked immunosorbent assay in frozen materials from 134 colorectal cancer patients who had received curative resections. Patients were divided into high expression and low expression groups based upon selected cut-off value. Correlations among PD-ECGF expression, clinicopathologic features, and disease-free interval were studied by univariate and multivariate analysis. To evaluate the origin of PD-ECGF, serial sections of the 134 tumours were stained for PD-ECGF and CD68. RESULTS: PD-ECGF expression in the normal mucosa was 34.4+/-15.5 (Units/mg protein) and the cut-off value was 65.4 (mean+2SD). There were no significant correlations between clinicopathological features and PD-ECGF expression. The disease-free interval for the high PD-ECGF expression group was significantly longer than that of the low expression group (P=0.05). A multivariate Cox's regression analysis revealed that high PD-ECGF expression is an independent factor for better outcome. In immunohistochemical study, almost all tumour cells were negative for PD-ECGF, but stromal macrophages were predominantly positive for PD-ECGF. CONCLUSIONS: The PD-ECGF expression originated from stromal macrophages was a predictor for favorable outcome after curative resections for colorectal cancer.
AIMS: We aim to clarify the long-term outcomes after an additional radical operation following gasless video endoscopic transanal rectal tumour excision (gasless VTEM) of 'high-risk' T1 and T2 rectal cancer. METHODS: Gasless VTEM involves modification of transanal endoscopic microsurgery (TEM) by incorporating a standard laparoscopic video camera without a CO(2) insufflation system. This study between 1993 and 2003 included six men and five women with a median age of 64 years (range, 36-79). Specimens resected by gasless VTEM revealed (1) high-risk T1 carcinomas with one of the following histological types: poorly differentiated, lymphovascular invasion, and massive invasion of the submucosa (submucosal invasion greater than 200-300 microm from the muscularis mucosa) and (2) T2 carcinomas. RESULTS: Eight patients had a high-risk T1 carcinoma and three patients had a T2 carcinoma. In two patients with a high-risk T1 carcinoma, a residual tumour was found in the specimen resected by the additional radical surgery. At a median follow-up of 86.5 months (range, 63.2-110.5), none of the patients developed tumour recurrence. Although one patient died with cancer at another organ site (hilar cholangiocarcinoma of the liver) 87 months after the additional radical surgery, the other 10 patients are alive and disease free. CONCLUSIONS: This study revealed favorable long-term outcomes after additional radical surgery following gasless VTEM in patients with high-risk T1 and T2 carcinomas.
AIMS: The new Japanese staging system for hepatocellular carcinoma (HCC), the Japan integrated staging (JIS) score, accounts for both Child-Pugh classification and Japan tumour node metastasis (TNM) staging. However, in HCC patients who undergo hepatectomy, liver function is relatively good and a better prognostic classification of hepatic function is necessary. METHODS: The present study was designed to analyse the modified JIS score using liver damage grade by the Liver Cancer Study Group of Japan instead of the Child-Pugh classification (using the category indocyanine green retention rate at 15 min [ICG(R15)] instead of encephalopathy), and to compare the Japan TNM stage in 101 patients who underwent resection of HCC. RESULTS: The liver damage grade showed significantly better discrimination of disease-free and overall survival than did the Child-Pugh classification. The modified JIS score system showed significant differences of disease-free and overall survivals in each score and this system was superior for discriminating survivals compared with the TNM staging. CONCLUSIONS: The combined staging system of hepatic function, particularly ICG(R15), and tumour stage provides a better prediction of prognosis. The JIS score using the liver damage grade was a useful predictor of prognosis of HCC patients who underwent hepatic resection.
BACKGROUND: The aim of this study is to determine whether gasless, video endoscopic transanal-rectal tumor excision (gasless VTEM) is a valid treatment for rectal carcinoid and laterally spreading tumors (LST). METHODS: Eighty-four patients with an adenoma, adenocarcinoma (Tis/T1), or carcinoid tumor of the rectum were divided into three groups: (i) LST ( n = 17 patients), (ii) carcinoid ( n = 11), and (iii) control with other types of tumors ( n = 56). RESULTS: The LST group had a longer median operating time than in the control group, whereas the carcinoid group had a shorter operating time. Two patients (11.7%) in LST group developed peritoneal entry during the operation, while 2 patients (3.6%) in the control group experienced postoperative complications. During a median follow-up length of 55.2 months, one patient in the LST group developed a recurrence. CONCLUSIONS: Gasless VTEM is a simple, minimally invasive procedure used to treat LST and carcinoid tumors of the rectum. However, resection for the LST group had a high risk of peritoneal entry during operation.
AIMS: The new staging system proposed by the Cancer of the Liver Italian Program (CLIP) for hepatocellular carcinoma (HCC) accounts for both liver dysfunction and tumour characteristics. The present study was designed to analyze UICC TNM stage, CLIP and modified CLIP in 91 patients who underwent hepatic resection for HCC. METHODS: In the modified CLIP, scoring of AFP was replaced by that of protein induced by vitamin K absence or antagonist II (PIVKA-II; predictive value, > or = 400 mAU/ml). RESULTS: After hepatic resection, 54 patients developed recurrent tumours. High PIVKA-II was a significant determinant of recurrence (p<0.05). However, a high score of the modified CLIP as well as those other staging systems did not correlate with tumour-recurrence rate. Univariate analysis showed that high TNM score, CLIP score and our modified CLIP score were significant predictors of poor prognosis. Multivariate Cox's analysis revealed that high PIVKA-II and high modified CLIP score were associated with higher risk for disease-free and overall survival as well as high TNM stage. CONCLUSIONS: Compared with the original CLIP, our modified CLIP was a better predictor of prognosis of HCC patients who underwent hepatic resection.
The chromosomal aberrations underlying the development of resistance to fluoropyrimidines have not yet been identified. To characterise the genomic changes that induce the development of resistance to fluoropyrimidines, we used comparative genomic hybridisation (CGH) to analyse and compare the parent DLD-1 human colorectal cancer cell line and two cell lines, DLD-1/5-FU and DLD-1/FdUrd, which were resistant to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd), respectively. Both resistant cell lines showed a genetic aberration derived from the parental cell line DLD-1. Losses of 3p and 3q were also detected as additional genetic changes in the two resistant cell lines. Both resistant cell lines showed decreased orotate phosphoribosyltransferase (OPRT) activity, which is associated with the activity of the uridine monophosphate (UMP) synthase gene (3q13). These results suggested that the loss of 3q might be a genetic change responsible for the decreased OPRT activity and fluoropyrimidine cytotoxic response in cancer cells. Amplification of 18p11.2-p11.3 containing the thymidine synthase (TS) gene (18p11.32) was observed only in the DLD-1/FdUrd-resistant cell line, which overexpresses TS. These findings suggested that 18p amplification represents a genetic change associated with the overexpression of the TS protein. Our results indicate that chromosomal aberrations identified by CGH could explain, at least in part, acquired fluoropyrimidine resistance.
BACKGROUND/AIMS: The aim of this study was to clarify long-term outcomes of endoscopic mucosal resection (EMR) using a modified Buess technique for mucosal gastric cancer. METHODS: The procedure included en bloc mucosal resection using a Buess-type rectoscope into the gastric lumen via a temporary gastrostomy under video camera guidance. We reviewed 5 patients who underwent this procedure between 1995 and 1997 with a single mucosal cancer of the stomach that was unsuitable for en bloc excision by endoscopic snare diathermy. RESULTS: All tumors were superficial elevated types (type 0-IIa) located in the middle third and posterior wall of the stomach. Median maximum tumor diameter was 2.2 (range 1.1-3.5) cm. There was no operative mortality. One patient developed a hemorrhagic gastric ulcer postoperatively. All tumors histologically showed curative potential of the mucosal resection without margin involvement. During a median follow-up period of 64 (50-77) months, none of the patients developed local recurrence. One patient had an early gastric cancer that metachronously developed at another stomach site. CONCLUSION: Intragastric EMR using a modified Buess technique appears to be a useful treatment for cure of mucosal gastric cancer for a limited group of patients unsuitable for complete en bloc excision by endoscopic snare diathermy.
Molecular genetics experiments using gene targeting and transgenic technology demonstrated the importance of alpha-calcium-calmodulin-dependent protein kinase II (alphaCaMKII) in long-term potentiation (LTP) and memory. Little information is available though on how CaMKII activity may be regulated in vivo. We show that estradiol benzoate activates CaMKII in a dose and time-dependent manner in mouse hippocampus after 30 min stimulation. The effect of estrogen is via a very rapid nongenomic mechanism that is blocked in vitro in hippocampal primary neurons by the pure estrogen receptor antagonist, ICI 182,780. These results suggest that estrogen action in the hippocampus is linked to CaMKII activation.
Although prenatal ultrasonographic (US) diagnosis has been reported in biliary atresia (BA), most cases are type I (correctable with cystic dilatation). We report three prenatal cases of type IIId BA (uncorrectable with cystic dilatation). Routine fetal US at 22 to 24 weeks of gestation showed two communicating cystic lesions 12 to 16 mm in diameter. On color Doppler US, the lesions were separate from the portal vein or hepatic artery. The size did not change during the prenatal period in any case. Choledochal cyst (CC) was considered the most likely diagnosis, although BA with cystic lesions was also considered. After birth, the patients developed acholic stools and prolonged neonatal jaundice. Hepatobiliary scintigraphy showed negative passage. Duodenal fluid showed a negative or slightly positive Gmelin test. The neonates underwent laparotomy at the age of 36, 46, and 32 days, respectively. Intraoperative cholangiography showed the gallbladder and slightly-dilated common-bile duct without entering the proximal or distal bile ducts in all cases. They were classified as type IIId BA and underwent excision of the cystic lesions and dissection of the portal bile-duct remnants, followed by hepatic portoenterostomy. Case 1 showed persistent jaundice and finally underwent liver transplantation (LTx), case 2 became anicteric. Case 3 remained jaundiced and is to undergo LTx. In conclusion, type IIId BA may be one of the differential diagnoses when a cystic lesion is detected under the hepatic hilum by fetal US. However, prenatal diagnosis of BA is still difficult with respect to differentiation from a CC or type I BA. Early postnatal diagnosis followed by immediate treatment is important, especially in type IIId BA.
BACKGROUND: Transanal endoscopic microsurgery (TEM) is unpopular because of its high cost and most surgeons' unfamiliarity with microscopic surgery. This report describes an experience with a modification of TEM, gasless video endoscopic transanal rectal tumour excision (gasless VTEM), which incorporates a standard laparoscopic video camera and requires no carbon dioxide insufflation system. METHODS: One hundred and one patients with 105 rectal tumours underwent gasless VTEM between 1993 and 2000. RESULTS: Histological examination revealed 18 adenomas, 75 carcinomas (Tis, 47; T1, 23; T2, five), 11 carcinoid tumours and one lymphoma. The median height above the dentate line and maximum tumour diameter was 5.0 (range 2-14) cm and 2.0 (range 0.4-8.0) cm respectively. The peritoneal cavity was opened intraoperatively in two patients. The median operating time was 53 (range 15-202) min. Bleeding, suture dehiscence and transient incontinence developed after operation in four patients. There was no operative death. Median hospital stay was 5 (range 1-21) days. Eleven patients with T1/T2 staging underwent subsequent radical resection. The median duration of follow-up was 52.3 months. One patient with a carcinoma developed a recurrence. CONCLUSION: Gasless VTEM is a feasible, safe and minimally invasive procedure for the treatment of selected rectal adenomas and early carcinomas. The suggested modifications may make the procedure more widely available.
A liquid chromatographic-tandem mass spectrometric (LC/MS-MS) method was developed for the simultaneous quantification of prostaglandin (PG) E(2), PGF(2alpha), 6-keto-PGF(lalpha) and thromboxane (TX) B(2). These eicosanoids and their deuterium derivatives, using as internal standards, were extracted by solid-phase extraction and analyzed using LC/MS-MS in the selected reaction-monitoring (SRM) mode. A good linear response over the range of 10 pg to 10 ng for each eicosanoid was demonstrated. The accuracy of added eicosanoids ranged from 94.1 to 106.6% and coefficients of variation ranged from 0.62 to 7.8%. Furthermore, we applied this method for the determination of eicosanoids in the human synovial cell-cultured medium, stimulated by lipopolysaccharide (LPS). LPS produced each eicosanoid and they increased in a time-dependent manner. The production levels after 24 h stimulation were 6-keto-PGF(1alpha) > PGE(2) > TXB(2) >> PGF(2alpha). This simultaneous quantification method is so useful to clarify the function of synovial cells in rheumatoid arthritis (RA).
OBJECTIVE: In order to elucidate which cytokine preferentially stimulates the synovium in patients with rheumatoid arthritis (RA), we investigated the roles of tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) using SCID mice engrafted with human RA tissue (SCID-HuRAg). METHODS: The SCID-HuRAg mice were prepared according to our previously described method. First, SCID-HuRAg mice were treated with chimeric anti-TNF-alpha monoclonal antibody (mAb, 100 microg/mouse) and histological changes were examined 4 weeks after the initial treatment. Secondly, a total of 100 microg of recombinant TNF-alpha or IL-6 (0.6 microg/h) was administered daily to mice using an osmium pump. The histological changes and serum cytokine levels were examined 4 weeks after the initial administration. Human immunoglobulin G (IgG) was administered to mice as a control. RESULTS: Synovial inflammatory cells were significantly decreased after the anti-TNF-alpha mAb treatment; conversely, the degree of synovial inflammation was significantly exacerbated by TNF-alpha administration. The levels of both IL-6 and TNF-alpha in sera were significantly increased by recombinant TNF-alpha administration, while TNF-alpha levels were unchanged by IL-6 administration. This suggests that TNF-alpha controls IL-6 production. Despite the profound changes in inflammation, we found no effects on bone and no articular cartilage damage was produced by TNF-alpha. CONCLUSION: This study provides strong evidence that TNF-alpha is a key molecule in the control of the inflammatory changes that occur in the RA synovium. In addition, TNF-alpha regulates IL-6 production. However, other inflammatory pathways independent of TNF-alpha may contribute to the bone and cartilage damage seen in RA.
This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence.
Early gastric cancer can be divided morphologically into two categories, penetrating growth type-A (Pen-A type) and other growth types (non-Pen-A types). Sialyl Lewis(x) antigen has been demonstrated to play an important role in tumor metastasis by serving as a functional ligand in the cell adhesion system. The aim of this study is to ascertain whether or not sialyl Le(x) antigen expression correlates with tumor growth patterns of early gastric carcinoma. An immunohistochemical assay was performed using monoclonal antibody CSLEX1 in 12 Pen-A type and 79 non-Pen-A type cancers. Scoring was based on the percentage of immunoreactive cells: negative, low expression (< or = 25%), and high expression (> 25%). Lymph node metastasis was found more frequently in Pen-A type than non-Pen-A type cancers (P=0.0004). Furthermore, sialyl Le(x) antigen high expression was detected more often in Pen-A type cancers (7 out of 12; 58.3%) than non-Pen-A type cancers (13 out of 79; 16.5%) (P=0.0036). Multivariate logistic regression analysis showed that these variables are related independently to the Pen-A type and the non-Pen-A type tumor growth patterns. These data suggest that the difference in sialyl Le(x) antigen expression between the Pen-A type and non-Pen-A type tumor growth patterns of early gastric cancer may, at least partially, reflect different biological behavior during tumor progression.
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