ABSTRACT
Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.
ABSTRACT
Cholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c-SRC, which are tumor-promoting genes. The FAXC/ANXA2/c-SRC complex forms in the mitochondria. FAXC enhances SRC-dependent ANXA2 phosphorylation at tyrosine-24, and the C-terminal amino acid residues (351-375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial-mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets.
Subject(s)
Annexin A2 , Bile Duct Neoplasms , Carcinogenesis , Cholangiocarcinoma , Mitochondria , src-Family Kinases , Animals , Humans , Male , Mice , Annexin A2/metabolism , Annexin A2/genetics , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/genetics , Carcinogenesis/genetics , Carcinogenesis/metabolism , Cell Line, Tumor , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Mitochondria/metabolism , Phosphorylation , Signal Transduction , src-Family Kinases/metabolism , src-Family Kinases/geneticsABSTRACT
Gastric cancer is the fifth most common malignancy worldwide. However, targeted therapy for advanced gastric cancer is still limited. Here, we report BEX2 (Brain expressed X-linked 2) as a poor prognostic factor in two gastric cancer cohorts. BEX2 expression was increased in spheroid cells, and its knockdown decreased aldefluor activity and cisplatin resistance. BEX2 was found to upregulate CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) expression, a cancer stemness-related gene, in a transcriptional manner, and the knockdown of which also decreases aldefluor activity. Collectively, these data are suggestive of the role of BEX2 in the malignant process of gastric cancer, and as a promising therapeutic target.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Prognosis , Cell Line, Tumor , Oncogenes , Nerve Tissue Proteins/metabolismABSTRACT
BACKGROUND: Exposure to environmental carcinogens, such as through smoking, is a major factor in the carcinogenesis of non-small cell lung cancer (NSCLC). However, genetic factors may also contribute. METHODS: To identify candidate tumor suppressor genes for NSCLC, we included 23 patients (10 related pairs and 3 individuals) with NSCLC who had other NSCLC-affected first-degree relatives in a local hospital. Exome analyses for both germline and somatic (NSCLC specimens) DNA were performed for 17 cases. Germline exome data of these 17 cases revealed that most of the short variants were identical to the variants in 14KJPN (a Japanese reference genome panel of more than 14 000 individuals) and only a nonsynonymous variant in the DHODH gene, p.A347T, was shared between a pair of NSCLC patients in the same family. This variant is a known pathogenic variant of the gene for Miller syndrome. RESULTS: Somatic genetic alterations in the exome data of our samples showed frequent mutations in the EGFR and TP53 genes. Principal component analysis of the patterns of 96 types of single nucleotide variants (SNVs) suggested the existence of unique mechanisms inducing somatic SNVs in each family. Delineation of mutational signatures of the somatic SNVs with deconstructSigs for the pair of germline pathogenic DHODH variant-positive cases showed that the mutational signatures of these cases included SBS3 (homologous recombination repair defect), SBS6, 15 (DNA mismatch repair), and SBS7 (ultraviolet exposure), suggesting that disordered pyrimidine production causes increased errors in DNA repair systems in these cases. CONCLUSION: Our results suggest the importance of the detailed collection of data on environmental exposure along with genetic information on NSCLC patients to identify the unique combinations that cause lung tumorigenesis in a particular family.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Dihydroorotate Dehydrogenase , Mutation , Carcinogenesis/genetics , GenomicsABSTRACT
In this study, a 76-year-old man initially diagnosed with branch-duct pancreatic intraductal papillary mucinous tumor is presented. During follow-up, stenosis was discovered in the main pancreatic duct of the tail. A nodular lesion was found in the pancreatic duct consistent with the stenosis. Distal pancreatectomy was performed since it was suspected to be malignant. Histopathology revealed polymorphic mononuclear cells proliferated with osteoclast-like giant cells in the nodule. The patient was finally diagnosed with anaplastic pancreatic cancer with osteoclast-like giant cells, a relatively rare tumor. It is reported herein with a review of the literature.
Subject(s)
Adenocarcinoma, Mucinous , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Adenocarcinoma, Mucinous/diagnostic imaging , Adenocarcinoma, Mucinous/surgery , Aged , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Constriction, Pathologic , Follow-Up Studies , Giant Cells/pathology , Humans , Male , Osteoclasts/pathology , Pancreatectomy , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Pancreatic NeoplasmsABSTRACT
Purpose: For incurable pancreatic cancer, the therapeutic goal is to prolong survival and maintain the quality of life (QOL). Unexpected outpatient consultation (OCT) and emergency hospitalization lead to QOL deterioration. The National Comprehensive Cancer Network (NCCN) guidelines recommend 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) and gemcitabine plus albumin-bound paclitaxel (nabPTX+GEM) as the preferred first-line regimens. Japanese clinical practice guidelines further recommend GEM and tegafur/gimeracil/oteracil potassium (S-1). Currently, no treatment strategy considers QOL at any stage during a patient's clinical course. Methods: In this study, hospital-free survival (HFS), defined as the period without hospitalization and OCT, was introduced as a new indicator of the qualitative aspect of overall survival (OS). We compared OS, length of hospitalization (LOH), OCT, and HFS for the four first-line chemotherapy groups. Results: No significant difference was observed in the median OS and HFS, nor was there a strong correlation between OS and LOH, based on the four first-line chemotherapy groups. In contrast, there were strong correlations between OS and OCT and between OS and HFS in all first-line chemotherapy groups. The ratio of OCT to OS was similar for mFOLFIRINOX and nabPTX+GEM. S-1 had the lowest OCT-to-OS ratio. The ratio of HFS to OS declined from highest to lowest in the order S-1, nabPTX+GEM, mFOLFIRINOX, and GEM. Conclusion: Our findings suggested existence of correlation differences between OS and HFS between first-line mFOLFIRINOX and first-line nabPTX+GEM. In addition, a good HFS was obtained with S-1 alone in some cases. In the future, clinical trials for chemotherapy should examine QOL during the entire clinical course.
ABSTRACT
Cancer stem cells (CSCs) are responsible for therapy resistance and share several properties with normal stem cells. Here, we show that brain-expressed X-linked gene 2 (BEX2), which is essential for dormant CSCs in cholangiocarcinoma, is highly expressed in human hepatocellular carcinoma (HCC) lesions compared with the adjacent normal lesions and that in 41 HCC cases the BEX2high expression group is correlated with a poor prognosis. BEX2 localizes to Ki67-negative (nonproliferative) cancer cells in HCC tissues and is highly expressed in the dormant fraction of HCC cell lines. Knockdown of BEX2 attenuates CSC phenotypes, including sphere formation ability and aldefluor activity, and BEX2 overexpression enhances these phenotypes. Moreover, BEX2 knockdown increases cisplatin sensitivity, and BEX2 expression is induced by cisplatin treatment. Taken together, these data suggest that BEX2 induces dormant CSC properties and affects the prognosis of patients with HCC.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/metabolism , Aged , Aldehyde Dehydrogenase/metabolism , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cholangiocarcinoma/metabolism , Cisplatin/pharmacology , Female , Gene Silencing , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Mice , Nerve Tissue Proteins/genetics , Organoids , Prognosis , Spheroids, CellularABSTRACT
Cancer stem cells (CSCs) are believed to cause cancer metastasis and recurrence. BEX2 (brain expressed X-linked gene 2) is a CSC-related gene that is expressed in dormant CSCs in cholangiocarcinoma and induces resistance against chemotherapy. The aim of the present study was to identify small compounds that have activity to inhibit BEX2 expression and result in the attenuation of CSC-related phenotypes. We screened 9600 small chemical compounds in high-throughput screening using cholangiocarcinoma cell line HuCCT1 expressing BEX2 protein fused with NanoLuc, and identified a compound, BMPP (1, 3-Benzenediol, [4-(4-methoxyphenyl)-1H-pyrazol-3-yl]). BMPP was found to exert decreasing effects on BEX2 protein expression and G0 phase population of the tumor cells, and increasing effects on ATP levels and chemotherapeutic sensitivity of the cells. These findings indicate that BMPP is a valuable chemical compound for reducing dormant CSC-related phenotypes. Thus, the identification of BMPP as a potential CSC suppressor provides scope for the development of novel therapeutic modalities for the treatment of cancers with BEX2 overexpressing CSCs.
Subject(s)
Antineoplastic Agents/analysis , Antineoplastic Agents/pharmacology , Drug Discovery , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/metabolism , Antineoplastic Agents/chemistry , Cell Line, Tumor , High-Throughput Screening Assays , Humans , Neoplastic Stem Cells/drug effects , Reproducibility of ResultsABSTRACT
Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.
Subject(s)
Bile Duct Neoplasms/metabolism , Cholangiocarcinoma/metabolism , Gene Expression Regulation, Neoplastic , Mitochondria/metabolism , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/metabolism , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Cullin Proteins/genetics , Cullin Proteins/metabolism , Humans , Mitochondria/genetics , Mitochondria/pathology , Nerve Tissue Proteins/genetics , Oxygen Consumption/physiologyABSTRACT
BACKGROUND: Accumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in human epithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC). METHODS: PDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined. RESULTS: Suppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis. CONCLUSIONS: CD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells.
Subject(s)
Antigens, CD/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Neoplasm Proteins/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Movement/genetics , Female , GPI-Linked Proteins/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Mice , Middle Aged , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , RNA, Small Interfering/pharmacology , Wound Healing , Xenograft Model Antitumor AssaysABSTRACT
The majority of cancer cells maintain a high glycolytic activity and an increased lactate production, even in a well oxygenated environment. This phenomenon is known as the Warburg effect. Previous studies have revealed that various types of cancer selectively express the pyruvate kinase M2 isoform (PKM2), and that PKM2 plays a pivotal role in the Warburg effect. Although elevated PKM2 levels have been observed in pancreatic cancer and other types of cancer, little is known about the biological function of PKM2. In this study, in order to examine the expression and role of PKM2 in pancreatic ductal adenocarcinoma (PDAC), we knocked down PKM2 in PDAC cells by introducing small interfering and short hairpin RNAs, and examined the gene expression profiles in the cells by microarray analysis. We analyzed the energy-producing pathways in the cells by XFe Extracellular Flux Analyzers, and detected intracellular metabolites by capillary electrophoresis time-of-flight mass spectrometry. We found that the RNAi-mediated knockdown of PKM2 diminished the proliferative, migratory and tumorigenic ability of the PDAC cell-lines. PKM2 knockdown also resulted in lower glycolytic activities and decreased levels of some intracellular metabolites, such as pyruvate and polyamine; however, it led to elevated levels of reactive oxygen species. Microarray analysis revealed the functional association between PKM2 and the expression of genes that drive the cell cycle. On the whole, the findings of this study demonstrate that PKM2 plays an important role in metabolic activities, as well as in the malignancy of PDAC cells.
Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Carrier Proteins/metabolism , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Pancreatic Neoplasms/pathology , Reactive Oxygen Species/metabolism , Thyroid Hormones/metabolism , Animals , Carcinogenesis/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/surgery , Carrier Proteins/genetics , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Profiling/methods , Gene Knockdown Techniques , Glycolysis/genetics , Humans , Isoenzymes/metabolism , Membrane Proteins/genetics , Metabolomics/methods , Mice, SCID , Pancreas/pathology , Pancreas/surgery , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/surgery , RNA, Small Interfering/metabolism , Thyroid Hormones/genetics , Xenograft Model Antitumor Assays , Thyroid Hormone-Binding ProteinsABSTRACT
Semaphorins and their receptors are abnormally expressed in various cancers, but little is known about the expression and function of semaphorin 3E (SEMA3E) and its receptor, plexin D1 (PLXND1), in gastric cancer development or metastasis. We evaluated SEMA3E and PLXND1 expression by quantitative RT-PCR in gastric tissues from 62 patients who underwent gastrectomy and analyzed the correlation between their expression and clinicopathological variables. To assess the function of SEMA3E, we generated human gastric cancer cell lines with suppressed or increased SEMA3E expression. The expression level of SEMA3E, but not PLXND1, was correlated with lymph node involvement and metastatic progression in gastric cancer. A significant association was observed between a high level of SEMA3E expression and poor differentiation or poor survival in the intestinal type of gastric cancer. SEMA3E knockdown in gastric cancer cells attenuated cell proliferation and metastatic ability in vitro and in vivo. Moreover, SEMA3E caused cell proliferation and anchorage-independent cell growth in the intestinal type of gastric cancer. These results suggested that SEMA3E is likely to be involved in the development of gastric cancer and might also be a therapeutic target for its treatment.
Subject(s)
Cell Adhesion Molecules, Neuronal/genetics , Semaphorins/genetics , Semaphorins/metabolism , Stomach Neoplasms/pathology , Up-Regulation , Animals , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins , Male , Membrane Glycoproteins , Mice , Neoplasm Metastasis , Neoplasm Transplantation , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Survival AnalysisABSTRACT
PURPOSE: This study aimed to establish an efficient strategy for screening and surveillance for occupational cholangiocarcinoma. METHODS: We evaluated the consecutive changes in laboratory findings during regular health examinations and in abdominal ultrasonography findings before the diagnosis of occupational cholangiocarcinoma in nine patients. The results of laboratory tests and abdominal ultrasonography at the time of diagnosis were also examined. RESULTS: In all patients, the serum γ-glutamyl transpeptidase (γ-GTP) activity increased several years before the diagnosis of cholangiocarcinoma. The serum alanine aminotransferase (ALT) activity also increased several years before the diagnosis, following an increase in the serum aspartate aminotransferase (AST) activity in most patients. Abdominal ultrasonography before the diagnosis revealed regional dilatation of the bile ducts, which continued to enlarge. At the time of diagnosis, the γ-GTP, AST, and ALT activities were increased in nine, seven, and seven patients, respectively. The regional dilatation of bile ducts without tumor-induced stenosis, dilated bile ducts due to tumor-induced stenosis, space-occupying lesions, and/or lymph node swelling were observed. The serum concentrations of carbohydrate antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) were increased in all patients. CONCLUSIONS: Regular health examinations with a combination of ultrasonography and laboratory tests including the γ-GTP, AST, ALT, CA 19-9, and CEA levels are useful for screening and surveillance for occupational cholangiocarcinoma.
Subject(s)
Bile Duct Neoplasms/chemically induced , Bile Duct Neoplasms/diagnosis , Cholangiocarcinoma/chemically induced , Cholangiocarcinoma/diagnosis , Early Detection of Cancer , Occupational Diseases/chemically induced , Occupational Diseases/diagnosis , Occupational Exposure/adverse effects , Solvents/adverse effects , Adult , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Bile Duct Neoplasms/prevention & control , Biomarkers, Tumor/blood , CA-19-9 Antigen/blood , Carcinoembryonic Antigen/blood , Cholangiocarcinoma/prevention & control , Humans , Male , Middle Aged , Occupational Diseases/epidemiology , Occupational Diseases/prevention & control , Ultrasonography , gamma-Glutamyltransferase/bloodABSTRACT
BACKGROUND: We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. METHODS: We examined the location and distribution of the carcinomas: atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of three patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. RESULTS: BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor-induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non-neoplastic biliary epithelium. CONCLUSIONS: The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging.
Subject(s)
Bile Duct Neoplasms/pathology , Bile Ducts/injuries , Bile Ducts/pathology , Cholangiocarcinoma/pathology , Occupational Diseases/pathology , Adult , Calcium-Binding Proteins/analysis , Diagnostic Imaging , Dilatation , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Proteins/analysisABSTRACT
Several recent studies have revealed that microRNAs (miRNAs) have a role in carcinogenesis and cancer development, and that it is stably detectable in plasma/serum. The aim of this study was to test whether miR483-3p as well as miR21 could be plasma biomarkers for PDAC. The plasma samples were obtained from three groups including 32 pancreatic ductal adenocarcinoma (PDAC) patients, 12 patients with intraductal papillary mucinous neoplasm (IPMN) patients and 30 healthy controls (HC). We evaluated the plasma miR483-3p and miR21 expression level by quantitative RT-PCR. We compared the differences in the plasma level of these miRNAs among the three groups, and investigated the relevance of their plasma expression level to the clinical factors in PDAC. The expressions of miR483-3p and miR21 were detected in all examined plasma samples. The plasma expression levels of these miRNAs were significantly higher in PDAC compared to HC (P<0.01). The plasma miR483-3p expression was significantly higher in PDAC patients than IPMN patients (P<0.05). The plasma miR21 level was associated with advanced stage (P<0.05), metastasis to lymph node and liver (P<0.01), and shorter survival (P<0.01) of the PDAC patients. Together, these findings suggest that measurement of the plasma miR483-3p level is useful for discriminating PDAC from IPMN, and that the plasma miR21 level predicts outcome of PDAC patients.
Subject(s)
Adenocarcinoma/genetics , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Pancreatic Ductal/genetics , MicroRNAs/biosynthesis , Pancreatic Neoplasms/genetics , Adenocarcinoma/blood , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Carcinoma, Intraductal, Noninfiltrating/blood , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Pancreatic Ductal/blood , Carcinoma, Pancreatic Ductal/pathology , Diagnosis, Differential , Female , Gene Expression Regulation, Neoplastic , Humans , Lymph Nodes , Male , MicroRNAs/blood , Middle Aged , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathologyABSTRACT
BACKGROUND: Cholangiocarcinoma has been reported in workers exposed to chlorinated organic solvents and has consequently been classified as an occupational disease (occupational cholangiocarcinoma) by the Japanese Ministry of Health, Labour and Welfare. This study aimed to identify the characteristics of nine workers newly diagnosed with occupational cholangiocarcinoma. METHODS: This study was a retrospective study conducted in 13 hospitals and three universities. Clinicopathological findings of nine occupational cholangiocarcinoma patients from seven printing companies in Japan were investigated and compared with 17 cholangiocarcinoma patients clustered in a single printing company in Osaka. RESULTS: Patient age at diagnosis was 31-57 years. Patients were exposed to 1,2-dichloropropane and/or dichloromethane. Serum γ-glutamyl transpeptidase activity was elevated in all patients. Regional dilatation of the intrahepatic bile ducts without tumor-induced obstruction was observed in two patients. Four patients developed intrahepatic cholangiocarcinoma and five developed hilar cholangiocarcinoma. Biliary intraepithelial neoplasia and/or intraductal papillary neoplasm of the bile duct was observed in four patients with available operative or autopsy specimens. CONCLUSIONS: Most of these patients with occupational cholangiocarcinoma exhibited typical findings, including high serum γ-glutamyl transpeptidase activity, regional dilatation of the bile ducts, and precancerous lesions, similar to findings previously reported in 17 occupational cholangiocarcinoma patients in Osaka.
Subject(s)
Bile Duct Neoplasms/diagnosis , Bile Ducts, Intrahepatic , Cholangiocarcinoma/diagnosis , Occupational Exposure/adverse effects , Printing , Adult , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/etiology , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/etiology , Diagnostic Imaging , Female , Follow-Up Studies , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Occupational Diseases , Retrospective Studies , Survival Rate/trendsABSTRACT
We reported a case of early cystic duct carcinoma concomitant with xanthogranulomatous cholecystitis (XGC). This case was a 72-year-old man in whom thickening of the gallbladder wall was pointed out an abdominal ultrasonography and elevation of the CA19-9 level was detected at a local clinic. Endoscopic ultrasonography and CT demonstrated a mass in the cystic duct. Mapping biopsy using peroral cholangioscopy (POCS) revealed a diagnosis of cystic carcinoma with superficial flat growth, therefore a pylorus-preserving pancreatoduodenectomy was performed. Histopathological diagnosis was well differentiated papillotubular adenocarcinoma with superficial flat spread and the thickening of the gallbladder wall was XGC. A case of early cystic duct carcinoma concomitant with XGC is extremely rare.
Subject(s)
Adenocarcinoma/complications , Bile Duct Neoplasms/complications , Cholecystitis/complications , Cystic Duct , Granuloma/complications , Xanthomatosis/complications , Adenocarcinoma/pathology , Aged , Bile Duct Neoplasms/pathology , Humans , MaleABSTRACT
A 53-year-old woman was referred to our hospital for further examination of a rectal polypoid lesion. Colonoscopy revealed a submucosal tumor in the rectum (Ra) and a diagnosis of MALT lymphoma was made on the histological examination of the biopsy specimens and Southern blot analysis of the immunoglobulin heavy chain gene rearrangement. Although the patient was negative for Helicobacter pylori, H. pylori eradication therapy was performed. Colonoscopy 3 months after the eradication therapy showed disappearance of the rectal tumor. H. pylori eradication appears to be a useful treatment for not only H. pylori-positive colonic MALT lymphoma but H. pylori-negative colonic MALT lymphoma.
Subject(s)
Anti-Infective Agents/administration & dosage , Lymphoma, B-Cell, Marginal Zone/drug therapy , Rectal Neoplasms/drug therapy , 2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Clarithromycin/administration & dosage , Drug Therapy, Combination , Female , Helicobacter pylori/drug effects , Helicobacter pylori/isolation & purification , Humans , Lansoprazole , Lymphoma, B-Cell, Marginal Zone/microbiology , Middle Aged , Rectal Neoplasms/microbiologyABSTRACT
In March, 2004, a 64-year-old man was given a diagnosis of IPMN of the pancreas in postoperative CT of left shoulder blade chondrosarcoma. In October, 2007, because a tumor in the pancreas body was found, distal pancreatectomy was performed a diagnosis of the poorly differentiated adenocarcinoma. Histopathologic diagnosis revealed as pancreatic endocrine tumor and immunity dyeing was useful for differential diagnosis. A case of pancreatic endocrine tumor developing from IPMN has a possibility not rare for frequency, but few reports are available so far.