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↗

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

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

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↗

PubMed2004

Expression of epidermal growth factor receptor, apomucins, matrix metalloproteinases, and p53 in rat and human cholangiocarcinoma: appraisal of an animal model of cholangiocarcinoma.

OBJECTIVE: We sought to determine the expression of molecular markers in an animal model of cholangiocarcinoma compared with those in human cholangiocarcinoma. SUMMARY BACKGROUND DATA: Cholangiocarcinoma is a rare disease characterized by early intrahepatic and extrahepatic spread, which seriously limits the efficacy of surgery. Establishing an experimental model to study the cholangiocarcinogenesis is desirable. METHODS: Sprague-Dawley rats weighing 300 +/- 50 g were used for the study group. The animals were given 0.3% thioacetamide in tap water continuously. Thirty mass-forming peripheral cholangiocarcinoma patients also were studied. Expression of epidermal growth factor receptor (EGFR), MUC1, MUC2, MUC5AC, MMP-2, MMP-9, and p53 in both human and experimental rat cholangiocarcinoma was examined using immunohistochemistry. RESULTS: Using thioacetamide 0.3% as a hepatoxin to induce cholangiocarcinoma in rats, microfoci of cancerous cells were detected from 12 weeks, and all experimental rats displayed diffuse mass-forming cholangiocarcinoma after 24 weeks. EGFR was strongly expressed in 14 (47%) of 30 human cholangiocarcinoms and 24 (100%) of 24 rat cholangiocarcinomas, respectively. MUC1 was strongly expressed in all human and rat cholangiocarcinomas, whereas MUC2 and MUC5AC were focally and weakly expressed. MMP-2 and MMP-9 were strongly expressed in 22 (73%) of 30 human cholangiocarcinomas and 24 (100%) of 24 rat cholangiocarcinomas, respectively. p53 overexpression was detected in 9 (30%) of 30 human cholangiocarcinoma and none of the rat cholangiocarcinoma, respectively. CONCLUSIONS: The expression of EGFR, apomucins, MMPs, and p53 in rat cholangiocarcinoma was strongly homologous to human cholangiocarcinoma. Thioacetamide-induced cholangiocarcinoma in rats provides an excellent model for investigating cholangiocarcinogenesis in vivo.

Animals↗

PubMed2004

Hepatic resection of the intraductal papillary type of peripheral cholangiocarcinoma.

BACKGROUND: Peripheral cholangiocarcinoma (PCC) can be grossly classified into mass-forming, periductal-infiltrating, and intraductal papillary (IP) types. Information on IP-PCC patients undergoing hepatectomy is sparse because of the small number of cases. METHODS: The clinical features of 40 IP-PCC patients undergoing hepatectomy between 1977 and 2000 were reviewed. The clinical features of 94 PCC patients without IP growth undergoing hepatectomy were used for comparison. RESULTS: IP-PCC and non-IP-PCC groups had similar age distributions (P =.674), sex ratios (P =.079), and positive rates for serum carcinoembryonic antigen and CA 19-9 (P =.121 and.795, respectively). The two groups also exhibited similar rates of association between hepatolithiasis and PCC (P =.230). However, more IP-PCC patients exhibited signs during admission, and more had ALT values >36 IU/L; they also had smaller tumors, more mucobilia association, and tumors in earlier stages and had undergone more postoperative chemotherapy. Multivariate logistic regression analysis showed that only ALT >36 IU/L differentiated IP-PCC from non-IP-PCC patients. The two groups exhibited similar operative mortality (P = 1.0). Follow-up ranged from 1.6 to 125.2 months (mean and median, 44.6 and 5.7 months, respectively). The 1-, 3-, and 5-year overall survival rates were 72.9%, 41.2%, and 24.7%, respectively, in the IP-PCC group and 43.3, 6.03%, and 2.01% in the non-IP-PCC group. The prognosis was favorable for the IP-PCC patients (P <.00001), particularly for IP-PCC patients who received curative hepatectomy (P =.013). CONCLUSIONS: IP-PCC patients had significantly better survival than non-IP-PCC patients, and aggressive curative hepatic resection is associated with a longer survival.

Adult↗

PubMed2004

Breast reconstruction with a muscle-sparing free transverse rectus abdominis myocutaneous flap: comparison between immediate and delayed groups.

BACKGROUND: Breast reconstruction offers not only physical but also psychological rehabilitation. Autologous tissue transfer is a good option for breast reconstruction. The purpose of this study was to investigate the success rate, complications, and cosmetic outcomes following use of a muscle-sparing free transverse rectus abdominis myocutaneous (TRAM) flap for breast reconstruction. METHODS: Between August 1999 and February 2001, 15 consecutive patients underwent breast reconstruction using a muscle-sparing free TRAM flap after a mastectomy. Ten patients received mastectomies and immediately underwent breast reconstruction using muscle-sparing free TRAM flaps at Chang Gung Memorial Hospital. The remaining 5 patients first received a modified radical mastectomy and then underwent breast reconstruction. RESULTS: The mean age of patients was 43.9 (range, 32 to 50) years. Ten patients (67%) underwent immediate reconstructions, and 5 (23%) underwent delayed reconstructions. The overall success rate was 93.3%. Postoperative complications included 1 abdominal seroma and 1 small area of breast fat necrosis. Six of 10 patients with immediate reconstruction underwent both adjuvant chemotherapy and hormone therapy, while 3 patients received only chemotherapy. None of these adjuvant therapies were delayed by the reconstructive surgery. At a mean follow-up of 26.7 months, no local recurrence had been found, and 93% of patients were satisfied with the esthetic results. CONCLUSIONS: A muscle-sparing free TRAM flap is a good option for breast reconstruction. Both the success rate and patient satisfaction are high. The subsequent adjuvant therapy need not be delayed following immediate reconstruction.

Adult↗

PubMed2003

Expression of Bcl-2 family modulated through p53-dependent pathway in human hepatocellular carcinoma.

The biological behavior of hepatocellular carcinoma (HCC) is, in part, relevant to apoptosis. A systematic investigation of the apoptosis-related Bcl-2 family modulated by p53 in HCC is lacking. A total of 22 HCC patients were studied. The expression of p53 protein in HCC was assessed using the immunohistochemical method, which categorized the HCC patients into two groups: group 1, with immunonegative p53 (N = 7); and group 2, with immunopositive p53 (N = 15). The expression of p53, p21, Bcl-2, Bax, Bcl-xL, and Bcl-xS in the 22 HCC cases detected by western bioting was quantified with a densitometer. The apoptosis of the 22 HCC cases was determined by terminal deoxynucleotidyltransferase-mediated UTP end-labeling (TUNEL). We found that Bcl-2 was remarkably up-regulated in group 2 (14 of 15), but was down-regulated in group 1 (5 of 7). Bax was up-regulated in both group 1 (6 of 7) and group 2 (13 of 15). Bcl-xL was up-regulated in both group 1 (5 of 7) and group 2 (9 of 15). Bcl-xS was remarkably down-regulated in group 2 (14 of 15) compared to group 1 (4 of 7). The apoptosis indexes of groups 1 and 2 were 0.82 +/- 0.26% and 0.33 +/- 0.17%, respectively (P = 0.023). The long-term survival of group 1 was superior to that of group 2 (log-rank test, P = 0.001). In conclusion, Bcl-2 and Bcl-xS represented the most significant anti- and proapoptotic proteins, respectively, modulated through a p53-dependent pathway in HCC.

Apoptosis↗

PubMed2003

Expression of deleted in malignant brain tumor-1 (DMBT1) molecule in biliary epithelium is augmented in hepatolithiasis: possible participation in lithogenesis.

Deleted in malignant brain tumor-1 (DMBT1) is a mucin-like molecule participating in mucosal immune defense. Given that bovine gallbladder mucin, which accelerates cholesterol crystallization, is a DMBT1 homolog, DMBT1 expression was examined immunohistochemically in biliary epithelial cells in livers with hepatolithiasis (N = 25), primary sclerosing cholangitis (N = 7), large bile duct obstruction (N = 12), and control normal livers (N = 10). DMBT1 protein was determined in the hepatic bile samples of hepatolithiasis (N = 12) and other hepatobiliary diseases (N = 8) by immunoblot. While DMBT1 was faintly expressed in normal livers (20%), it was significantly augmented in hepatolithiasis (76%) (P < 0.05). DMBT1 was mildly expressed in primary sclerosing cholangitis and large bile duct obstruction. DMBT1 protein was detected frequently in hepatic bile samples of hepatolithiasis (50%) (P < 0.05), but in the other bile samples. The percentage of cholesterol in intrahepatic calculi was significantly higher in the patients with DMBT1-positive bile. Augmented expression and secretion of DMBT1 in intrahepatic large bile ducts in hepatolithiasis suggests its role in lithogenesis.

Agglutinins↗

PubMed2003

Laparoscopic resection of malignant gastric polyp-with a particular emphasis on localization by laparoscopic ultrasonography.

Adenomatous polyps of the stomach are rare and usually found on routine endoscopic examination. These polyps should be removed because of their potential for malignant transformation. Endoscopic polypectomy is the preferred treatment modality, but a laparotomy is required to resect large polyps. This study presents a case of a large gastric polyp containing carcinoma in situ that was successfully managed by laparoscopic gastrectomy. With the use of a novel technique, the tumor was localized by intraoperative laparoscopic ultrasonography. The patient had an excellent postoperative recovery, and follow-up endoscopy at 24 months revealed no recurrent tumor.

Adenoma↗

PubMed2003

Profiling of gene expression associated with hepatolithiasis by complementary DNA expression array.

By use of cDNA expression array method, we compared the expression profiles of genes in hepatolithiasis tissues with those of paired normal tissues. Expression of 1176 cancer related genes that include 33 tumor suppressor genes, 100 proto-oncogenes and 37 DNA damage repair genes were examined in this study. We found that expression of tumor suppressor genes and proto-oncogenes was systemically activated in hepatholithiasis tissues, suggesting that expression of genes controlling cell growth becomes unstable in liver lobe of hepatolithiasis. In contrast, expression of DNA damage repair genes were not activated but rather remained unchanged in hepatholithiasis tissues, suggesting that repair process is not strongly activated but rather impaired in hepatholithiasis tissues.

Calculi↗

PubMed2002

Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver.

Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression.

Adult↗