Blastic natural killer (NK) cell lymphoma is a rare neoplasm characterized by blastoid tumor cells expressing CD4 and CD56, with predominant skin involvement. Although this tumor has been regarded as a neoplasm related to NK cell, recent studies suggested that it is derived from plasmacytoid dendritic cells, but not from NK cell. Herein we report 4 cases of CD4+CD56+ lineage marker- blastic NK cell lymphomas with a review of literatures. The patients were 3 men and one woman. Three of them were young (17, 18, and 22 yr old). Three patients had skin lesions, at initial presentation in two patients and during the course of disease in other patient. Histologically, tumors consisted of monotonous medium to large blastoid cells showing no necrosis, angiocentric growth or epidermotrophism. All four tumors were CD4+ and CD56+. Three expressed CD68 antigen. Lineage specific markers for B- and T cell were negative. All tumors did not express myeloperoxidase. T-cell receptor gene rearrangement, EBV, CD13 and CD33 were negative. In one patient, tumor cells arranged in Homer-Wright type pseudorosette and expressed terminal deoxynucleotidyl transferase(TdT). Despite the standard lymphoma chemotherapy, the tumors, except one lost during follow-up, progressed and relapsed. The patients died 8-60 months after diagnosis.
Adolescent ; Antigens, CD4/*analysis ; Antigens, CD56/*analysis ; Cell Lineage ; Female ; Humans ; Killer Cells, Natural/immunology/*pathology ; Lymphoma, T-Cell/immunology/*pathology ; Male ; Middle Aged

BACKGROUND/AIMS: Common bile duct ligation will induce cholestatic fibrosis or cirrhosis in the rat. However, the degree of histologic changes following ligation of the common bile duct appears to vary widely due to recanalization of the bile duct in the distensible extrahepatic system. The purpose of this study is to compare liver damages induced by traditional simple ligation of bile duct with those induced by ethanolic sclerosis of bile duct and ligation. METHODS: Twenty rats of 7 weeks-aged Spraugue-Dawley (body weight 200~250 gm) were divided into 2 groups, common bile duct ligation (BDL group n=10), and 60% ethanol infusion into the common bile duct before bile duct ligation (ETL group n=10). After 7 weeks, all animals were sacrificed. Gross findings, histologic findings (Ki-67 and Masson- trichrome staining), and liver function test were compared. RESULTS: During the experiment, 5 rats of BDL group and 4 rats of ETL group died. In the operative findings, diameter of bile duct in BDL group was dilatated 8~15 mm, but there was no dilatation in ETL group. In the histologic findings of extrahepatic bile duct, epithelial cells were maintained well in BDL group, but they were all cast off or destroyed in ETL group. Liver fibrosis and cell proliferation are more prominent in the ETL group. Also, ETL group showed worse liver function test than that of BDL group. CONCLUSION: Liver fibrosis or cirrhosis by prolonged bile duct ligation is a well-known experimental model. In this study, we demonstrated that a new method of bile duct ligation (ethanol infusion before bile duct ligation) which abolishes bile duct distention accompanied with simple bile duct ligation is more effective to produce liver fibrosis or cirrhosis.
Animals ; Bile Ducts* ; Bile Ducts, Extrahepatic ; Bile* ; Cell Proliferation ; Common Bile Duct ; Dilatation ; Epithelial Cells ; Ethanol* ; Fibrosis ; Ligation ; Liver Cirrhosis* ; Liver Function Tests ; Liver* ; Models, Theoretical* ; Rats ; Sclerosis*

PURPOSE: Cyclooxygenase-2 (COX-2) expression is up-regulated in several types of human cancers and it has been suggested that COX-2 is closely inked to carcinogenesis. The objectives of this study were to investigate COX-2 expression in periampullary cancer and to evaluate the association of the clinicopathological factors with its expression. METHODS: Thirty specimens which were resected from patients with periampullary cancers (13 pancreatic adenocarcinomas, 8 common bile duct cancers, 9 ampulla of vater cancers) were investigated by immunohistochemical staining using Anti COX-2 monoclonal Ab. The 30 specimens were divided into stain-positive and stain-negative groups. The correlation between COX-2 expression and the various clinicopathological factors including the tumor size, nodal metastasis, differentiation, perineural and vascular invasion, were studied. RESULTS: COX-2 was expressed in 69% of pancreatic adenocarcinomas, 100% of common bile duct cancers and 78% of ampulla of vater cancers. However there was no significant correlation between COX-2 expression and the clinicopathological factors. CONCLUSION: COX-2 is highly expressed in periampullary cancer. Even though there was no correlation with the clinicopathological factors, the utility of the COX-2 inhibitors in preventing or treating periampullary cancer remains undetermined but warronts further investigation.
Adenocarcinoma ; Ampulla of Vater ; Carcinogenesis ; Common Bile Duct ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase 2* ; Humans ; Ink ; Neoplasm Metastasis

Patients with early gastric cancer (EGC) may be associated with an increased risk of having a second primary cancer. Metachronous primary malignancies may have an influence on the long term prognosis of these patients. We report here on two cases of bile duct cancer after performing subtotal gastrectomy for EGC. A 59-year-old man underwent pylorus preserving pancreaticoduodenectomy (PPPD) under the diagnosis of bile duct cancer, and this was done 5 years after he had undergone gastrectomy. The pathological specimens were different between the EGC and bile duct cancer according to their morphology and immunohistochemical staining, and this case was determined to be metachronous double cancer. The second case was a 39-year-old man who received PPPD for bile duct cancer 4 years after undergoing gastrectomy. Double primary malignancies of bile duct cancer and gastric cancer are very rare.
Adult ; Bile ; Bile Duct Neoplasms ; Bile Ducts ; Gastrectomy ; Humans ; Middle Aged ; Neoplasms, Second Primary ; Pancreaticoduodenectomy ; Prognosis ; Pylorus ; Stomach Neoplasms

Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology characterized by adult onset, an absence of autoantibodies, inflammatory bowel disease, and a loss of interlobular bile ducts. In the present report, a case fulfilling the IAD criteria is described. A 19-year-old man was admitted to the hospital for persistent elevation of transaminases and alkaline phosphatase without clinical symptoms. Viral hepatitis markers and autoantibodies were absent. The patient had a normal extrahepatic biliary tree and had no evidence of inflammatory bowel disease. A liver biopsy specimen showed absence of interlobular bile ducts from 58% of the portal tracts. He was diagnosed with IAD and was treated with ursodeoxycholic acid.
Adult ; Cholestasis, Intrahepatic/*diagnosis/etiology/pathology ; Chronic Disease ; Humans ; Male

BACKGROUND/AIMS: The incidence of duodenal tumors has increased by health surveillance. However, preoperative diagnosis of subepithelial duodenal tumors remains difficult because of the wide variety of pathologies and the location of the tumors. We analyzed endoscopic, radiological, and pathological features of subepithelial benign duodenal tumors (BDTs), which were treated by surgical resection. METHODS: Five patients with subepithelial BDTs treated by surgical resection were analyzed retrospectively. We compared the preoperative and postoperative diagnosis and evaluated the clinical presentations, endoscopic and radiological findings, surgical treatments, pathological results, and outcomes of these patients. RESULTS: All the patients underwent successful surgical resection. There were two cases of gastrointestinal stromal tumors (GISTs) treated with segmental duodenectomy, one case of carcinoid tumor treated with antrectomy, one case of gangliocytic paraganglioma treated with ampullectomy, and a lipoma removed by mass excision. The two GISTs were in the duodenal third and fourth segment close to the pancreas, and it was difficult to exclude pancreatic tumors by imaging studies. All the patients remained healthy for more than three years. CONCLUSIONS: Subepithelial BDTs are rare and difficult to diagnosis. Awareness and preoperative diagnosis of subepithelial BDTs can lead to minimally invasive treatment, including endoscopic or local surgical resection.
Carcinoid Tumor ; Diagnosis ; Duodenum ; Gastrointestinal Stromal Tumors ; Humans ; Incidence ; Lipoma ; Pancreas ; Paraganglioma ; Pathology ; Retrospective Studies

BACKGROUND/AIMS: It is well known that alcohol enhances the toxicity of CCl4. We tried to establish an alcoholic liver cirrhosis model by administration of alcohol and CCl4 to rats. We also wanted to know the hepatoprotective effect of low doses of lipopolysaccharide(LPS) in this animal model. METHODS: Of 20 female adult rats, 8 were ingested with alcohol ad libitum(group 1) Another 6 were ingested with 10% alcohol and 50% 1mL/kg CCl4 intragastrically by Sonde twice a week(group 2) The remaining 6 were ingested with 10% alcohol, CCl4, and 0.1mg/kg LPS intraperitoneally twice a week(group 3) The fibrosis was evaluated semiquantitatively on a scale of 0(none) to 3(cirrhosis). RESULTS: 1) After 10 weks, septal fibrosis or cirrhosis was produced in 9 out of 12 rats in groups 2 and 3 but there was no fibrotic change in group 1. 2) There was no significant difference in pathological grading between groups 2 and 3. CONCLUSIONS: Hepatic fibrosis or cirrhosis can be sufficiently induced by alcohol and repetitive CCl4 ingestion for 10 weeks. We can not prove the hepatoprotective effect of low dose LPS by semiquantitative evaluation of pathological grading.
Animals ; Carbon Tetrachloride Poisoning/*complications ; English Abstract ; Ethanol/*toxicity ; Female ; Lipopolysaccharides/*administration & dosage ; Liver/pathology ; Liver Cirrhosis, Alcoholic/pathology/*prevention & control ; Rats ; Rats, Sprague-Dawley

BACKGROUND/AIMS: Local drug delivery to the bile duct may be effective to prevent proliferative cholangitis (PC) through capability of high dose administeration with minimal systemic side effects. Paclitaxel is an anticancer drug whose side effect on the stabilization of microtubule leads to cell death. The aims of this study were to establish the proliferative cholangitis model in rat, mimicking biliary stricture in human, and to test whether paclitaxel-coated nylon thread prevents biliary stricture in a PC model of rat. METHODS: PC was induced by introducing a fine nylon thread into the bile duct in a rat from 1 week to 4 week. To evaluate the effects of paclitaxel as a locally-delivered anti-proliferative drug, dog gallbladder epithelial cells were exposed to sequential concentrations of paclitaxel (0.1microM, 1microM, 10microM, and 100microM) for 20 min. in vitro, and inhibition of proliferation was measured by (3)H-thymidine uptake assay. Paclitaxel- coated 5-0 nylon threads (1.8+/-0.5 ug/3 cm thread, measured by HPLC) were made by immersion of ethanolic paclitaxel (50 mg/ml) and evaporation of the solvent. Nylon threads were inserted into the bile duct of male Sprague-Dawley rats weighing 200~50 g. Paclitaxel (n=15) and control (n=15) groups were divided with or without paclitaxel-coating procedure. The paclitaxel effects were assessed by histomorphological examination one week after thread implantation. RESULTS: The decrease of (3)H-thymidine uptake was observed at 100microM of paclitaxel exposured for 20 minutes in the presence of epidermal growth factor (50 nM/ml) than control. PC model characterized by epithelial-glandular proliferation and fibrous thickening of the bile duct wall through 1~ week. This model was established at 1 week. The effect of paclitaxel-coated nylon thread into the bile duct were evaluated after 1 week. In paclitaxel treated the luminal area, luminal length and the ratio of lumen to bile duct cross sectional area increased by 276% (p=0.044), 87% (p=0.012) and by 330% (p=0.000), respectively, versus control. The total wall area, epithelial-glandular area, and stromal area were similar between paclitaxel treated group and control (p>0.05). The bile duct wall thickness of paclitaxel group decreased by 33% (p=0.011, 273 (90)microM vs 410 (95)microM, paclitaxel vs control). CONCLUSION: Paclitaxel-coated nylon thread into bile duct was effective for the suppression of luminal stenosis, and may offer a therapeutic option for biliary stricture and biliary stricture associated disease.
Animals ; Bile Ducts ; Cell Death ; Cholangitis* ; Constriction, Pathologic ; Dogs ; Epidermal Growth Factor ; Epithelial Cells ; Ethanol ; Gallbladder ; Humans ; Immersion ; Male ; Microtubules ; Nylons* ; Paclitaxel ; Phenobarbital ; Rats* ; Rats, Sprague-Dawley

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases. PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/alpha-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/alpha-SMA(high) or PDPN-/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.
Actins/immunology/*metabolism ; Adult ; Aged ; Aged, 80 and over ; Antibodies/immunology ; Carcinoembryonic Antigen/blood ; Colorectal Neoplasms/*diagnosis/mortality/pathology ; Disease-Free Survival ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Membrane Glycoproteins/immunology/*metabolism ; Middle Aged ; Neoplasm Staging ; Phenotype ; Prognosis ; S100 Proteins/immunology/*metabolism ; Tumor Markers, Biological/metabolism

PURPOSE: VEGF-C and VEGF-D are angiogenetic factors, and abnormal expression of E-cadherin hasa role in the progression of gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of E-cadherin, VEGF-C and VEGF-D with the presence of lymph node metastases (LNM) using cytokeratin 18 in early gastric cancer (EGC). MATERIALS AND METHODS: Immunohistochemical staining for E-cadherin, VEGF-C and VEGF-D was performed in 49 EGC patients from March 1997 to December 2002. To evaluate the real extent of LNM, 1,562 lymph nodes from 49 patients were re-examined with the use of cytokeratin 18. RESULTS: Eleven (0.7%) LNM were newly found in 12.2% (n=6) of patients. The real LNM rate was 3.6% in mucosal invasive (m) cancer and 38.1% in submucosal invasive (sm). Stage migration was seen in three patients (6.1%). Abnormal expression of E-cadherin was detected in 36.7% of the patients and expression of VEGF-C and VEGF-D was detected in 16.3% and 36.7% of the patients, respectively. Abnormal expression of E-cadherin was significantly correlated with tumor differentiation (P=0.0103) and Lauren classification (P<0.0001). There was no positive relationship of VEGF-C and VEGF-D expression with the clinicopathological findings for EGC including LNM. However, the frequency of lymph node metastases was significantly higher in patients that demonstrated abnormal expression of E-cadherin with positive immunoreactivity of VEGF-C or VEGF-D (P=0.031). CONCLUSION: In present study, we could not demonstrate a relationship between the presence of LNM and expression of VEGF-C and VEGF-D in EGC. However, VEGF-C or VEGF-D expression, in addition to the abnormal expression of E-cadherin, was correlated with the real extent of LNM in EGC.
Cadherins ; Humans ; Keratin-18 ; Keratins ; Lymph Nodes ; Neoplasm Metastasis ; Stomach Neoplasms ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D