Biomedical subjects

Ta-Sen Yeh

Publications and source records attributed to Ta-Sen Yeh.

At least 19 recordsLinked to original sources

PubMed2026

KRAS Expression Complements Genomic Profiling in Identifying Therapeutic Vulnerability in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains a major therapeutic challenge. Although alterations in the RAS pathway occur in over 50% of tumors, only a limited proportion are clinically actionable. We investigated whether KRAS expression complements genomic profiling for patient stratification and therapeutic vulnerability in GC. METHODS: Comprehensive genomic profiling was performed in 19 Taiwanese GC patients and compared with TCGA-STAD data (n = 434). KRAS mRNA expression and overall survival were evaluated by meta-analysis of 13 independent cohorts (n = 2,521). Protein-level validation was performed by immunohistochemistry in an independent cohort (n = 121). Functional KRAS dependency and response to combined MEK/SHP2 inhibition were assessed in eight GC cell lines. RESULTS: KRAS amplification was entirely contained within the KRAS-high population, whereas most KRAS-high tumors lacked detectable amplification. High KRAS expression was associated with poorer overall survival (HR 1.23, p = 0.001) and remained an independent prognostic factor after multivariable adjustment (adjusted HR 1.24, p = 0.003). Protein-level analysis showed a concordant trend. KRAS expression correlated strongly with functional dependency (R2 = 0.88, p = 0.005), was enriched in MSI and CIN subtypes, and identified cell lines with enhanced sensitivity to combined MEK/SHP2 inhibition. CONCLUSIONS: KRAS expression complements genomic profiling by identifying biologically relevant KRAS-dependent GCs beyond mutation or amplification alone. Integrating expression-based stratification with genomic profiling may improve patient selection for RAS pathway-directed combination therapies.

Biomarker↗

PubMed2007

Identification of NV-F virus DNA in hepatocellular carcinoma.

A fragment of DNA sequence derived from a hepatotropic virus, named NV-F was isolated recently. The aim of this study was to examine whether this virus was associated with hepatocellular carcinoma (HCC). Total cellular DNA was extracted from hepatocellular carcinoma tissues. NV-F virus DNA was detected by PCR. The PCR products were subjected to sequence analysis. Of the 78 HCC samples included, 12 (15.4%) were positive for NV-F virus DNA. Sequence analysis of the 12 amplified DNA fragments revealed a point mutation in one of them. The clinicopathological parameters between patients with and without NV-F virus infection were compared. It was found that patients with NV-F virus infection were older than those without NV-F virus infection (mean ages, 61.5 versus 52.5 years; P = 0.032). Otherwise, no difference was observed between the two groups. Of the 12 HCC patients positive for NV-F virus DNA, 11 patients were co-infected by either hepatitis B or C virus. The remaining patient was a Taiwanese aboriginal inhabitant with cryptogenic cirrhosis. In conclusion, NV-F virus DNA was identified in 15.4% of HCC tissues. HCC patients with NV-F virus infection were significantly older than those without NV-F virus infection.

Carcinoma, Hepatocellular↗

PubMed2006

Identification of a novel actin isoform in hepatocellular carcinoma.

OBJECTIVE: Altered actin isoform expression occurs in some pathological conditions including muscular malignancies. This study was to investigate whether a similar event occurs in hepatocellular carcinoma. METHODS: Cellular RNA was extracted from cancerous and non-cancerous hepatoma tissues. Reverse transcription (RT)-PCR followed by cloning and sequencing was performed to obtain populations of actin sequences. Phylogenetic analysis was carried out to identify novel actin isoforms. Interaction between the novel actin isoform and other cellular proteins was examined by the yeast two-hybrid system. The relative amounts of the novel actin isoform in the cancerous and non-cancerous tissues were further assayed using real-time PCR with specific primers. RESULTS: When compared between the cancerous and non-cancerous tissues, the proportion of non-beta-actins in the cancerous parts increased significantly in three of four cases included. Among the non-beta-actins, a novel group of isoforms was identified, temporarily named kappa-actins. Two genetically closely related sequences, FKSG30 and an actin-like sequence in the Cat Eye syndrome region, were found to cluster with the kappa-actins. Protein interaction assay indicated that the interaction between kappa-actin and prefoldin 2 was greatly diminished. The relative amounts of kappa-actin increased in 12 of 20 cancerous tissues assayed. CONCLUSIONS: A novel class of actin isoforms was expressed in some hepatocellular carcinoma tissues, replacing beta-actins to become the major constituents of actin cytoskeleton.

Journal Article↗

PubMed2006

Cholangiographic spectrum of intraductal papillary mucinous neoplasm of the bile ducts.

OBJECTIVE: To propose a cholangiographic classification for intraductal growth type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor, collectively termed intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B). SUMMARY BACKGROUND DATA: For the extensive clinicopathologic variations of IPMN-B, a detailed characterization of cholangiography for IPMN-B is beneficial for determining the optimal therapeutic strategy. METHODS: A total of 124 patients with cholangiography-available and pathologically proven IPMN-B were retrospectively studied. Numbers of IPMN-B type 1, type 2, type 3, and type 4 were 33, 17, 15, and 59, respectively. A cholangiographic classification was proposed based on the presence of hepatolithiasis, mucobilia, neoplasia localization, and concomitant malignancies. The demographics, histologic grading, management, and survival were also analyzed. RESULTS: All 33 IPMN-B type 1 and 12 of 17 IPMN-B type 2 displayed cholangiographic pattern IA demonstrating hepatolithiasis-related biliary stricture. The remaining 5 IPMN-B type 2 displayed cholangiographic pattern IB or IC, which demonstrated mucobilia without discernible neoplasia. Seven of 15 IPMN-B type 3 and 52 of the 59 IPMN-B type 4 displayed cholangiographic pattern IIA or IIB, which demonstrated overt intraductal neoplasia. Seven IPMN-B type 3 or 4 displayed cholangiographic pattern IIIA or IIIB, which demonstrated IPMN-B and concomitant malignancies. For those presenting with cholangiographic pattern IA, IC, IIA, IIB, and IIIA, straightforward hepatectomies for the diseased lobes were performed. For those with pattern IB, surgical resections were performed only when there was emergence of mucin-producing neoplasia. For those with IIIB, the concomitant malignancies were considered inoperable. No disease-related death occurred in IPMN-B type 1and 2. The mean survival rates of IPMN-B type 3 and type 4 were 55.5 +/- 17.1 months and 36.9 +/- 6.3 months, respectively. CONCLUSION: The presented cholangiographic classification facilitates the management for IPMN-B. Significant survival discrepancy at the various stages warrants a more aggressive surgical strategy.

Adenocarcinoma, Mucinous↗

PubMed2005

Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct--an immunohistochemical study of 110 cases of hepatolithiasis.

BACKGROUND/AIMS: Two types of neoplastic lesions preceding invasive intrahepatic cholangiocarcinoma (ICC) are identified: a flat-type neoplastic lesion called 'biliary intraepithelial neoplasia (BilIN)' and an intraductal papillary neoplasm of the bile duct (IPN-B). Multi-step carcinogenesis has been suggested in both lesions, although phenotypic changes during this process remain unclarified. METHODS: We immunohistochemically examined expression patterns of MUC1, MUC2, MUC5AC, cytokeratin 7 (CK7), and CK20 in BilIN, IPN-B, and ICC in 110 cases of hepatolithiasis. RESULTS: Thirty-seven cases of ICC in hepatolithiasis were divided into 18 tubular adenocarcinomas with BilIN, 10 tubular adenocarcinomas with IPN-B and nine colloid carcinomas with IPN-B. Carcinogenesis via BilIN was characterized by MUC2-/CK7+/CK20-with increasing MUC1 expression. IPN-B was characterized by the intestinal phenotype (MUC2+/CK20+), and carcinogenesis leading to tubular adenocarcinoma was associated with increasing MUC1 expression and that to colloid carcinoma with MUC1-negativity. Pathological stages of tubular adenocarcinoma of ICC with BilIN or IPN-B were more advanced than those of colloid carcinoma with IPN-B. CONCLUSIONS: Immunophenotypes of MUCs and cytokeratins might characterize three cholangiocarcinogenetic pathways in hepatolithiasis. Increased expression of MUC1 in BilIN and also IPN-B is associated with tubular adenocarcinoma, while colloid carcinoma in IPN-B is characterized by MUC1-negativity and less advanced pathologic stages.

Adenocarcinoma, Papillary↗

PubMed2005

High-frequency Alu-mediated genomic recombination/deletion within the caspase-activated DNase gene in human hepatoma.

The Alu repetitive elements, which constitute 10% of human genome, may serve as bridges for genomic recombination. However, their roles in tumorigenesis remain to be elucidated. Caspase-activated DNase (CAD), whose gene (hCAD) is mapped at chromosome 1p36, a region frequently displaying hemizygote deletion in many human cancers, is the key enzyme for nucleosome fragmentation during apoptosis. Recently, we detected many aberrant mRNAs for hCAD in many human hepatoma cells. To elucidate the genetic basis leading to the mRNA aberration, we used PCR-based chromosome walking to clone the corresponding genomic DNA identifying a novel Alu/Alu homologous recombination/deletion within hCAD in HepG2 and Hep3B cells. We then detected similar recombination events in 13 out of the 20 hepatoma tissues and in eight of the para-cancerous cirrhotic livers. The recombination was inclined to occur in males (P=0.031) and had marginal association with high-grade hepatoma (P=0.070) and tumor recurrence (P=0.070). The recombination caused exon-3 deletion, which in turn led to exon-3 skipping or replacement with a partial Alu-sequence, and consequential C-truncation of CAD. Our findings of high frequency of Alu-mediated hCAD deletion in human hepatoma not only underscore the implication of hCAD in hepatocarcinogenesis, but also highlight the potential roles of human repetitive sequences in mediating genome instability in human cancers.

Alu Elements↗

PubMed2005

Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: two decades of experience at Chang Gung Memorial Hospital.

AIM: To analyze the prognostic factors influencing the overall survival of peripheral cholangiocarcinoma (PCC) patients undergoing surgical treatment during 25 years at a single institution. METHODS: This study retrospectively reviewed prospectively collecting data about 373 patients with histologically proven PCC who underwent surgical treatment between 1977 and 2001. RESULTS: Three hundred and seventy-three PCC patients (159 men and 214 women) underwent surgical treatment from 1977 to 2001. Among them, 187 PCC patients underwent hepatectomy and 135 had curative resection (curative resectability rate: 36.2%). The follow-up duration ranged from 1.05 to 167.6 mo (mean/median = 14.1/7.2 mo). Overall cumulative survival rates at 1, 3, and 5 years were 32.5%, 9.2%, and 4.1%, respectively. Univariate log-rank analysis identified the following as adverse influences on overall survival: presence of symptoms, absence of mucobilia, elevated CEA and CA 19-9 levels, non-papillary tumor type, receiving non-hepatectomy, advanced tumor staging, lack of post-operative chemotherapy, and radiotherapy. Meanwhile, multivariate Cox's proportional hazard analysis demonstrated that absence of mucobilia, non-papillary tumor type, advanced tumor staging, non-hepatectomy, and lack of post-operative chemotherapy were the five independent prognostic factors that adversely affected overall survival. CONCLUSION: Favorable overall survival of PCC patients undergoing surgical treatment depends on early tumor stage, presence of mucobilia, papillary tumor type, hepatic resection, and post-operative chemotherapy.

Adenocarcinoma↗

PubMed2005

Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2.

We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.

Cholangiocarcinoma↗

PubMed2005

Significance of cellular distribution of ezrin in pancreatic cystic neoplasms and ductal adenocarcinoma.

HYPOTHESIS: Pancreatic cystic neoplasms and ductal adenocarcinoma manifest diverse clinical features and prognoses, which might be related to cellular distribution of ezrin modulated through various trophic molecules. DESIGN: Laboratory investigation and retrospective analysis. SETTING: Medical school-affiliated university hospital. PATIENTS AND METHODS: Patients with solid pseudopapillary tumor (SPT) (n = 12), mucinous cystic neoplasm (MCN) (n = 18), intraductal papillary mucinous tumor (IPMT) (n = 18), and ductal adenocarcinoma (PA) (n = 73) of the pancreas were studied. Expression of epidermal growth factor (EGF) and its receptor (EGFR) and ezrin were determined using immunohistochemistry. Epidermal growth factor receptor and ezrin expression in sodium butyrate (SB)-treated PA cell line PANC-1 was determined using immunocytochemistry. Messenger RNA expression of ezrin in the PANC-1 cell line treated with SB was determined using reverse transcriptase-polymerase chain reaction. Multivariate analysis of survival of patients with PA was performed. RESULTS: None of 12 SPTs displayed synchronous expression of EGF and EGFR, while all 3 malignant SPTs displayed membranous ezrin expression. One of 18 MCNs displayed synchronous expression of EGF and EGFR, while 4 of 6 borderline malignant and 8 of 8 malignant MCNs displayed membranous ezrin expression. Two of 4 borderline malignant and 11 of 11 malignant IPMTs displayed synchronous expression of EGF and EGFR, and all borderline malignant and malignant IPMTs displayed membranous ezrin expression. Less differentiated PA displayed EGF, EGFR, and membranous ezrin expression more frequently compared with more differentiated PA. Epidermal growth factor receptor expression of PANC-1 cells decreased in an SB dose dependent manner, in which PANC-1 cells became more differentiated and membranous ezrin expression of PANC-1 cells decreased correspondingly. Messenger RNA expression of ezrin in PANC-1 cells also decreased in an SB dose dependent manner. Patients with PA with membranous ezrin expression had a poorer prognosis compared with those without (P = .02). CONCLUSIONS: Membranous translocation of ezrin might play a role during malignant transformation of SPT, MCN, IPMT, and PA, which are either dependent on (IPMT and PA) or independent of (SPT and MCN) the EGF-EGFR pathway. Membranous ezrin expression represents a prognostic factor for PA.

Adenocarcinoma, Mucinous↗

PubMed2005

Characterization of intrahepatic cholangiocarcinoma of the intraductal growth-type and its precursor lesions.

A cohort of patients with intraductal growth-type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor lesions, collectively termed intraductal papillary neoplasm of the liver (IPNL), was characterized with respect to demographics, clinical manifestations, perioperative management, long-term survival, and molecular features associated with carcinogenesis. A total of 122 patients with IPNL types 1 through 4, 108 patients with non-IG-ICC and 210 patients with hepatolithiasis alone were studied. Expression of CDX2, TFF1, MUC1, MUC2, MUC5AC, EGFR, and p53 was determined by using immunohistochemistry. Females predominated in those with hepatolithiasis alone and IPNL. The mean age of patients with hepatolithiasis alone was 6 to 8 years younger than that of those with IPNL. The association with hepatolithiasis in patients with IPNL types 1 and 2, IPNL types 3 and 4, and non-IG-ICC was 100%, 79%, and 64%, respectively. Mucobilia, anemia, and elevated serum carcinoembryonic antigen levels were helpful in distinguishing IG-ICC and its precursor lesions. The mean survival of patients with IPNL type 3, IPNL type 4, and non-IG-ICC was 55.5 months, 36.9 months, and 15.8 months, respectively. The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3. Expression and cellular distribution of MUC2 and CDX2 were similar. MUC5AC was strongly expressed in all patients with IPNL; EGFR and p53 were rarely expressed in patients with IPNL. In conclusion, hepatolithiasis appears to be a precipitating factor in the development of IPNL. Signs of mucobilia were specific for the diagnosis of IPNL. Expression of CDX2 and MUC2 are helpful in differentiating IPNL and non-IG-ICC. Significant differences in survival associated with the various lesions studied warrants a more aggressive surgical strategy in their management.

Bile Duct Neoplasms↗

PubMed2005

Gallbladder carcinoma with biliary invasion: clinical analysis of the differences from nonbiliary invasion.

Gallbladder carcinoma is the most common malignancy of the biliary tract. Because of a lack of specific presentations, this condition frequently is diagnosed only at an advanced stage. The clinical difference between gallbladder carcinoma with and without biliary involvement remains uncertain. This study recruited all patients with gallbladder carcinoma treated at Chang Gung Memorial Hospital (Taoyuan, Taiwan) from 1987 to 2002. The sample included 120 patients aged 28 to 91 years (mean 65.5 +/- 12.3 years) (39 men, 81 women), whose medical records were reviewed retrospectively. Based on the 2002 newly revised TNM classification, 25, 38, 28, and 29 patients had stage I, II, III, and IV disease, respectively. After we excluded patients with stage I, the other patients were classified into two groups as follows: group I, gallbladder carcinoma with biliary invasion (n = 41); group II, carcinoma without biliary involvement (n = 54). The clinical presentations, laboratory data, operative methods, and outcome of these two groups were compared. The two groups did not differ in terms of age, sex distribution, cholelithiasis, and most clinical presentations. Chemistry laboratory data also identified patients in group I with significantly elevated liver function tests. Group II had a borderline tendency toward better curative resectability than group I (p = 0.09). Survival was significantly better for group I patients who underwent curative resection (n = 5) via cholecystectomy, partial hepatectomy, and bile duct resection than for those with noncurative resection (p < 0.05). However, long-term survival demonstrated that gallbladder carcinoma had the same poor prognosis in the two groups. In conclusion, gallbladder carcinoma with biliary invasion has been found to a more overt clinical presentation and abnormal laboratory data, which might alert clinicians to consider gallbladder carcinoma at an advanced stage or biliary invasion and examine the underlying disease. Generally, the outcome of gallbladder carcinoma is dismal, and radical curative resection combined with cholecystectomy, partial hepatectomy, and bile duct resection perhaps may offer good benefits for advanced gallbladder carcinoma. Furthermore, surgical resection should be performed whenever possible in patients with gallbladder carcinoma to increase life expectancy.

Adult↗

PubMed2005

Clinicopathological factors predicting long-term overall survival after hepatectomy for peripheral cholangiocarcinoma.

Peripheral cholangiocarcinoma (PCC) is clinically challenging because patients typically do not present until the disease is relatively advanced. Three-year to 5-year survival rates even with resection thus remain dismal. This study aimed to determine the clinicopathological factors for predicting overall survival longer than 5 years in PCC patients treated with hepatectomy. From 1977 to 1997, the clinicopatholgical features of 11 PCC patients who underwent hepatectomy with long-term overall survival (group A) were reviewed. Comparison was made with the clinical features and factors influencing the outcome of 70 PCC patients who survived less than 5 years after hepatectomy (group B). Of 81 PCC patients undergoing hepatectomy, 11 (13.6%) were 5-year survivors. The 81 PCC patients comprised 32 men and 49 women, with a mean age of 56.0 years (range: 34-83 years). Univariate analysis showed that female gender, absence of physical findings, a higher percentage of presence of mucobilia, early staged tumor, intraductal papillary tumor growth, and curative hepatic resection were more frequent in group A patients than group B patients. However, multivariate logistic regression analysis showed that absence of physical findings, presence of mucobilia, early staged tumor, and curative hepatic resection were the four independent factors differentiating group A from B patients. The 1-, 3-, 5-, and 10-year survival rates of the group A patients were 100%, 100%, 100%, and 40%, whereas those of the group B patients were 46.0%, 9.5%, 0%, and 0%, respectively. Absence of physical findings, presence of mucobilia, early staged tumor, and curative hepatectomy could independently predict PCC patients with long-term overall survival after hepatectomy.

Aged↗

PubMed2005

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-beta1 by overexpression of cyclin D1.

Transforming growth factor-beta1 (TGF-beta1) is involved in tumor progression by promoting angiogenesis or suppressing the immune system; yet TGF-beta1 also has a growth-inhibitory effect on epithelial cells including carcinoma cells. Several mechanisms of impaired TGF-beta1 responsiveness of carcinoma cells have been reported. In this study, we examined how TGF-beta1 participates in the development and progression of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis, and how ICC cells escape from growth inhibitory effect of TGF-beta1. A total of 40 cases of hepatolithiasis were studied, including 16 cases of ICC, and in vitro studies were conducted with cultured murine non-neoplastic biliary epithelial cells (MBEC) and three ICC cell lines. Immunohistochemically, TGF-beta1 was expressed in mononuclear cells and mesenchymal cells around the stone-containing bile ducts and invasive ICC, and also in biliary epithelial cells (hyperplastic and precursor lesions, and ICC). TGF-beta type II receptor (TbetaR-II) was constantly expressed on biliary epithelial cells irrespective of biliary lesions. In cell culture studies, TGF-beta1 significantly inhibited proliferation of MBEC via downregulation of cyclin D1, cdk4, and cdk6, while TGF-beta1 did not influence the proliferation of ICC cells. After suppression of cyclin D1 expression in one ICC cell line using cyclin D1 small interfering RNA, TGF-beta1 significantly inhibited the proliferation of ICC cells. In conclusion, high levels of TGF-beta1 around ICC or its precursors may be involved in development and progression of ICC in hepatolithiasis. ICC cells could escape the growth inhibitory effect of TGF-beta1 by overexpression of cyclin D1.

Cell Division↗

PubMed2005

Aberrant expression of cdx2 homeobox gene in intraductal papillary-mucinous neoplasm of the pancreas but not in pancreatic ductal adenocarcinoma.

OBJECTIVES: The authors investigated differential expression of cdx2 in intraductal papillary mucinous neoplasm of the pancreas (IPMN) and ductal adenocarcinoma. METHODS: Patients with IPMN (n = 23) and pancreatic ductal adenocarcinoma (n = 30) were studied. Expression of cdx2 mRNA, CDX2 protein, muc2 mRNA, MUC2 apomucin, and MUC5AC apomucin were determined. RESULTS: Of 23 IPMN, expression of cdx2 was detected in 8 of 9 adenomas, 6 of 8 borderline malignancies, and 3 of 6 malignancies, respectively. Of the 3 cdx2-expressing malignant IPMN, 2 did not display CDX2 expression. The appearance of CDX2-positive neoplastic cells in IPMN coincided with that of MUC2-positive neoplastic cells. All 23 IPMN displayed a positive MUC5AC expression irrespective to the status of CDX2 expression. Of 30 ductal adenocarcinomas, none displayed cdx2, CDX2, and MUC2 expression, while 10 cases displayed positive MUC5AC expression. CONCLUSION: Aberrant expression of cdx2 homeobox gene was detected in IPMN but not in ductal adenocarcinoma, which might determine their diverse carcinogenesis.

Adenocarcinoma↗

PubMed2004

MUC1, MUC2 and MUC5AC expressions in cardiac myxoma.

BACKGROUND: Cardiac myxoma, the most common primary tumor of the heart, has a variable clinical presentation and immunohistochemical profile. An abundant mucopolysaccharidic matrix exists, including mucin, within cardiac myxoma. This investigation first reports the expressions of mucin genes in cardiac myxoma. METHODS: A retrospective study was conducted between December 1976 and February 2003, comprising 101 consecutive patients with cardiac myxoma who were treated with surgical excision. Detailed clinical parameters also were reviewed. Mucin genes, namely MUC1, MUC2 and MUC5AC, were studied immunohistochemically in 47 randomly selected patients. RESULTS: The study group contained 57 (57%) women and 44 (43%) men, with a mean age of 38+/-21 years. Their presentations included: asymptomatic (41%), dyspnea (35%), stroke (23%), chest pain (7%), fever (6%), syncope (5%) and tricuspid regurgitation (70%). The sample included 90 myxoma located in the left atrium, 3 (3%) recurrent myxoma and 8 (8%) myxoma not located in the left atrium. The myxoma did not differ with location or clinical event in terms of pathological scores, such as vascular proliferation, inflammation, cellularity, hyaline, calcification and thrombosis. Cardiac myxoma is characterized by excessive mucus secretion. Expression of membrane-associated MUC1 was considerably higher than that of the secreted mucins, MUC2 and MUC5AC (P<0.05). Furthermore, expression of MUC5AC is related to lesser embolism (P<0.05). CONCLUSIONS: This work first examined the immunohistochemical expression of mucin (MUC1, MUC2 and MUC5AC) in cardiac myxoma. This investigation then showed that the expression of representative membrane-associated mucin, MUC1, and/or secretory mucins, MUC2 and MUC5AC, in cardiac myxoma was associated with important tumor clinicopathological characteristics. Moreover, MUC5AC appears related to lesser embolism. This approach can help distinguish the potential roles of secretory mucins versus membrane-associated mucins in the development of cardiac myxoma.

Adolescent↗

PubMed2004

Thalidomide salvages lethal hepatic necroinflammation and accelerates recovery from cirrhosis in rats.

BACKGROUND/AIMS: The authors investigated the feasibility of thalidomide employed to treat liver fibrosis. METHODS: A cirrhotic model was established using Sprague-Dawley rats fed thioacetamide. Thalidomide-treated group was given thalidomide (10mg/kg/day) intraperitoneally for 10 consecutive days. Mortality, histopathological changes, TNFalpha, TGFbeta1, TIMP-1 and TIMP-2 were determined. Expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from the experimental rats were determined. RESULTS: The mortality rates of thalidomide-treated group and vehicle-treated group were 8 and 32%, respectively. The total Knodell score of thalidomide-treated rats was lower than those of vehicle-treated rats. Micro-nodular cirrhosis resolved grossly in thalidomide-treated rats on day 28; while vehicle-treated rats continued to display uneven liver surface on day 28. Expression of TNFalpha, TGFbeta1, TIMP-1, and TIMP-2 was decreased in thalidomide-treated rats compared to those treated with vehicles. Finally, the expression of TNFalpha and TGFbeta1 mRNA of Kupffer's cells derived from rats treated with thalidomide were much lower than those treated with vehicle. CONCLUSIONS: Thalidomide salvages lethal hepatic necroinflammation, accelerates recovery from cirrhosis in rats, and works by suppressing of TNFalpha and TGFbeta1 production of Kupffer's cells.

Animals↗

PubMed2004

Aberrant expression of CDX2 is closely related to the intestinal metaplasia and MUC2 expression in intraductal papillary neoplasm of the liver in hepatolithiasis.

Intraductal papillary neoplasia of the liver (IPNL) frequently presents gastrointestinal metaplasia with aberrant expression of MUC2 and MUC5AC and oversecretion of mucin into the ductal lumen. In this study, the involvement of CDX2, a homeodomain protein involved in the regulation of intestinal development and differentiation, in the expression of MUC2 was examined in mucinous intrahepatic cholangiocarcinoma (ICC) (n=7) and IPNL with hepatolithiasis (n=19) with comparison to conventional ICC (n=11), and intraductal papillary mucinous tumor and invasive ductal carcinoma of the pancreas (n=9 and 11, respectively). A total of 33 cases of hepatolithiasis, extrahepatic biliary obstruction and normal livers were used as the control. Immunohistochemically, both MUC2 and MUC5AC were frequently expressed in mucinous ICC and IPNL, while expression of MUC2 was not seen in conventional ICC. The nuclear expression of CDX2 was closely associated with the expression of MUC2 in mucinous ICC and IPNL. This intimate association of MUC2 and CDX2 was confirmed by double immunostaining. The cytoplasmic CDX2 expression was frequent in the mucinous and the conventional ICC and pancreatic carcinoma, irrespective of MUC2 and MUC5AC expression. CDX2 mRNA was detected in neoplastic cells showing cytoplasmic as well as nuclear expression of CDX2 by reverse transcriptase-polymerase chain reaction. One IPMT expressed MUC2 associated with nuclear CDX2 expression, while the other IPMT and conventional pancreatic carcinoma expressed MUC5AC only. Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous ICC and IPNL associated with hepatolithiasia, suggesting its role in intestinal differentiation and its association with carcinogenesis in these tumors.

Adult↗

PubMed2004

Endo-GIA for ligation of dilated cystic duct during laparoscopic cholecystectomy: an alternative, novel, and easy method.

BACKGROUND: This study prospectively assessed the efficacy and applicability of Endo-GIA for difficult and dilated cystic duct (CD) closure in 24 patients undergoing laparoscopic cholecystectomy (LC) due to CD stone. METHODS: From January 1998 to December 2002, 3325 patients underwent LC for gallbladder lesions at the department of general surgery at Chang Gung Memorial Hospital (Taipei, Taiwan), and 24 (0.72%) were identified as having dilated and difficult CD, which were ligated by Endo-GIA. This study prospectively followed these 24 patients and evaluated the management outcomes. The indications for LC in the 24 patients were symptomatic gallstones with or without common bile duct (CBD) stones (11 patients), Mirizzi syndrome type I (two patients), acute cholecystitis (five patients), acute cholecystitis with acute cholangitis (two patients), acute cholangitis (one patient), biliary pancreatitis (two patients), and gallbladder polyp (one patient). RESULTS: No patients required conversion to open surgery. The CD were successfully ligated with Endo-GIA in all 24 patients with dilated and difficult CD during LC. The postoperative course was uneventful except in two patients. One patient suffered bile duct injury (Stewart-Way class II), and was managed successfully by repeated endoscopic stent. The other case was complicated with retained CBD stone due to migration of fragmented CD stone and was managed by endoscopic papillotomy and stone retrieval. Followup ranged from 1 to 40.2 months (median, 18.5 months) and no other complications were discovered during the followup period. CONCLUSIONS: Endo-GIA is a safe and effective procedure for closing dilated and difficult CD. Endo-GIA could alternatively be attempted in other selected cases because of its ease of application.

Adult↗