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1.
Int J Clin Exp Pathol ; 8(5): 5848-55, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26191308

RESUMO

Intraductal papillary neoplasm of the bile duct (IPNB) exists in a pathway of multistep-carcinogenesis toward cholangiocarcinoma. Four subtypes are observed in IPNB, pancreatobiliary type, intestinal type, gastric type, and oncocytic type, similarly to the corresponding disease in the pancreas, intraductal papillary mucinous neoplasm (IPMN). IPNB can present with or without macroscopically visible mucin secretion. IPNB usually progresses to tubular adenocarcinoma. However, there are a limited number of well-described cases of gastric-type IPNB progressing not to tubular adenocarcinoma but to colloid carcinoma. Herein, we present a case of an 82-year-old female patient with gastric-type IPNB in the intrapancreatic common bile duct without macroscopically visible mucin secretion, which progressed to colloid carcinoma. As IPNB, especially without visible mucin secretion, is considered to be a heterogeneous group of diseases, such an unexpected association could occur.


Assuntos
Adenocarcinoma Mucinoso/patologia , Neoplasias do Ducto Colédoco/patologia , Ducto Colédoco/patologia , Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/cirurgia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Ducto Colédoco/química , Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/química , Neoplasias do Ducto Colédoco/genética , Neoplasias do Ducto Colédoco/cirurgia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Pancreaticoduodenectomia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
Int J Clin Oncol ; 20(4): 736-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25348194

RESUMO

BACKGROUND: Present-day diagnostic modalities for detecting periampullary carcinoma are suboptimal, and currently used proven markers lack specificity and sensitivity. METHODS: In order to assess the diagnostic potential of sperm protein 17, a cancer testis antigen, quantitative real-time PCR was performed to evaluate the expression of sperm protein 17 in tissue and sera specimens collected from periampullary carcinoma patients and normal subjects. Additionally, circulating levels of anti-sperm protein 17 antibodies were determined in sera of periampullary carcinoma patients and normal subjects using ELISA. RESULTS: Aberrant expression of sperm protein 17 was found in 14/15 (93 %) periampullary cancer tissues when compared with distant matched nonmalignant tissues (P = 0.006, Mann-Whitney U test). None of the distant matched nonmalignant tissues showed increased expression of sperm protein 17 mRNA. Area under the curve, sensitivity, and specificity were 0.791, 87, and 73 %, respectively. Increased levels of sperm protein 17 mRNA were demonstrated in sera of periampullary carcinoma patients (P = 0.020, Student's t test). Circulating levels of anti-sperm protein 17 antibody were found to be significantly elevated in 27/30 (90 %) periampullary carcinoma patients (P < 0.001, Student's t test). Area under the curve, sensitivity, and specificity were 0.954, 86.7, and 96.3 %, respectively. Only two of the normal subjects (7 %) showed elevated levels of anti-sperm protein 17 antibody. CONCLUSION: For the first time, our findings suggest that high levels of sperm protein 17 mRNA as well as increased circulating anti-sperm protein 17 antibodies can be used to distinguish periampullary cancer patients from healthy individuals, highlighting the diagnostic potential of sperm protein 17.


Assuntos
Ampola Hepatopancreática , Antígenos de Superfície/biossíntese , Biomarcadores Tumorais/biossíntese , Proteínas de Transporte/biossíntese , Neoplasias do Ducto Colédoco/metabolismo , Antígenos de Neoplasias/sangue , Autoanticorpos/sangue , Proteínas de Ligação a Calmodulina , Ducto Colédoco/química , Ducto Colédoco/imunologia , Neoplasias do Ducto Colédoco/sangue , Neoplasias do Ducto Colédoco/imunologia , Humanos , Masculino , Proteínas de Membrana , RNA Mensageiro
3.
Hum Pathol ; 45(5): 1109-14, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24656321

RESUMO

We present the first case of peripheral T-cell lymphoma, not otherwise specified expressing follicular helper T-cell markers with different histologic features simultaneously involving the common bile duct and pericholedochal lymph nodes in a 72-year-old woman patient. Abdominal computed tomography revealed a localized wall thickening in the common bile duct. With the impression of cholangiocarcinoma, pancreaticoduodenectomy was done. Microscopically, dense small lymphoid cells with only minimal cytologic atypia were observed with occasional lymphoepithelial-like lesions, whereas many atypical large cells infiltrated the pericholedochal lymph nodes. Immunohistochemically, most small cells in the bile duct and the large atypical cells in the lymph nodes were all reactive for follicular helper T-cell markers including CD4, PD-1, and CXCL-13. BIOMED-2 based polymerase chain reaction using the DNA template from either the bile duct lesion or the lymph node revealed identical but different dominant clonal peaks, indicating these 2 lesions represent a spectrum of the same disease.


Assuntos
Neoplasias do Ducto Colédoco/imunologia , Neoplasias do Ducto Colédoco/patologia , Linfoma de Células T Periférico/imunologia , Linfoma de Células T Periférico/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Idoso , Antígenos CD/análise , Ducto Colédoco/química , Ducto Colédoco/imunologia , Ducto Colédoco/patologia , Feminino , Humanos , Imunofenotipagem , Linfonodos/imunologia , Linfonodos/patologia , Tomografia Computadorizada por Raios X
4.
JOP ; 14(1): 71-3, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23306338

RESUMO

CONTEXT: Mixed adenoendocrine tumors of the extrahepatic bile ducts are exceedingly rare and most of those who are rarely diagnosed are adenocarcinomas. Neuroendorine tumors accounts for only 0.2-2%. CASE REPORT: We report a case of mixed adenoneuroendo-carcinoma of the common bile duct in an 82-year-old male. CONCLUSION: Clinical experience suggests that the neuroendocrine component of mixed tumors behave more aggressively than the regular biliary adenocarcinoma component. This clinical behavior may have an important role in the management of this clinical entity.


Assuntos
Neoplasias do Ducto Colédoco/diagnóstico , Ducto Colédoco/patologia , Tumor Misto Maligno/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Idoso de 80 Anos ou mais , Cromogranina A/análise , Ducto Colédoco/química , Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/metabolismo , Neoplasias do Ducto Colédoco/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Tumor Misto Maligno/metabolismo , Tumor Misto Maligno/cirurgia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/cirurgia , Sinaptofisina/análise , Resultado do Tratamento
5.
JOP ; 14(1): 85-7, 2013 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-23306342

RESUMO

CONTEXT: Carcinoid tumors arising from the bile ducts account for only a small fraction of biliary tract cancers. CASE REPORT: We report herein a 42-year-old man with a carcinoid tumor of the common bile duct. He presented with abdominal pain, bloating and dyspepsia. Clinicolaboratory and imaging studies suggested a probable obstructive common bile duct lesion. The patient underwent an endoscopic retrograde cholangiopancreatography with a stent placement in view of common bile duct decompression. Persistence of symptoms prompted a laparotomy and pancreaticoduodenectomy that revealed a well-differentiated carcinoid tumor originating in the common bile duct. CONCLUSION: Clinician's familiarity with the unusual sites of origin of neuroendocrine tumors and/or atypical presentation of such tumors may facilitate their early recognition and allow for a timely intervention.


Assuntos
Tumor Carcinoide/diagnóstico , Neoplasias do Ducto Colédoco/diagnóstico , Ducto Colédoco/patologia , Adulto , Tumor Carcinoide/metabolismo , Tumor Carcinoide/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Cromograninas/análise , Ducto Colédoco/química , Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/metabolismo , Neoplasias do Ducto Colédoco/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pancreaticoduodenectomia , Sinaptofisina/análise
6.
Hepatogastroenterology ; 59(113): 26-30, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22251519

RESUMO

BACKGROUND/AIMS: There was no data about endocrine cells in the extrahepatic bile duct in secondary cholangitis due to obstructive jaundice. The aim of the present study is to investigate immunohistochemically the endocrine cell types in the lower part of the human common bile duct in biopsy samples, collected during drainage because of complete or incomplete obstruction, caused mainly by stones. We explained the presence of various hormone-producing endocrine cells in this region with the regulation of physiological and pathological processes there. METHODOLOGY: We used light and electron microscopic immunohistochemistry. RESULTS: More gastrin-positive, somatostatin-positive, secretin-positive, serotonin-positive, chromogranin- A-positive and synaptophysin-positive endocrine cells were found compared to control preparations. CONCLUSIONS: Occurrence of endocrine cells may relate to disturbed bile flow and to formation of calculi. Endocrine cell hyperplasia may be related to longstanding inflammation as in chronic cholecystitis and all secreted hormones from the described ECs can support pathologic process in the choledochus, i.e. inflammation, increased mucus secretion, fibrosis, muscle contraction, etc. We may state that various ECs (similar to those in duodenum) present in the lower part of the large bile duct and their hormones exert action on physiology (motility, secretion) and pathology (inflammation and fibrosis) in that part of the biliary tree.


Assuntos
Coledocolitíase/patologia , Ducto Colédoco/patologia , Células Endócrinas/patologia , Icterícia Obstrutiva/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Bulgária , Coledocolitíase/complicações , Coledocolitíase/metabolismo , Coledocolitíase/cirurgia , Cromogranina A/análise , Ducto Colédoco/química , Ducto Colédoco/cirurgia , Drenagem , Células Endócrinas/química , Feminino , Gastrinas/análise , Humanos , Imuno-Histoquímica , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/metabolismo , Icterícia Obstrutiva/cirurgia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Secretina/análise , Serotonina/análise , Somatostatina/análise , Sinaptofisina , Proteínas de Transporte Vesicular/análise
7.
Appl Immunohistochem Mol Morphol ; 15(3): 299-304, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17721275

RESUMO

Many patients with pancreatic carcinoma have stent placement for biliary obstruction before resection. Stent-associated atypia, found in common bile duct (CBD) margins at the time of resection, may be confused with malignancy. We evaluated histologic and immunohistochemical changes in CBD margins from resection specimens for pancreatic carcinoma. Histologic findings in CBDs, including ulcer and inflammation; epithelial metaplasia, atypia, and gland complexity; and increased wall thickness, nerve entrapment, and smooth muscle content, were compared in 30 stented and 31 nonstented CBD margins from pancreaticoduodenectomies for carcinoma and 13 normal CBDs from autopsy material. The proliferation index was calculated for stented and nonstented CBDs after Ki-67 immunohistochemical staining. Immunostaining for Ki-67, p53, and c-erbB-2 was performed in stented CBDs and corresponding carcinomas. All the histologic changes occurred more frequently in stented and nonstented CBD margins from carcinoma patients than in normal CBDs. Stented CBDs had significantly increased epithelial changes and Ki-67 proliferation rate as compared with nonstented CBDs. The stented CBDs had significantly less p53 and c-erbB-2 expression as compared with corresponding pancreatic carcinomas. Caution should be applied when interpreting atypia in CBD margins from patients with a history of CBD stenting. Changes found in stented CBDs are characteristic, and in most cases can be distinguished from malignancy. In difficult cases, immunohistochemistry may be useful.


Assuntos
Carcinoma/patologia , Ducto Colédoco/patologia , Neoplasias Pancreáticas/patologia , Stents/efeitos adversos , Carcinoma/química , Proliferação de Células , Ducto Colédoco/química , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Neoplasias Pancreáticas/química , Receptor ErbB-2/análise , Proteína Supressora de Tumor p53/análise
8.
World J Gastroenterol ; 12(19): 3038-43, 2006 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-16718784

RESUMO

AIM: To determine whether gastric and enteric Helicobacter species are associated with pancreatic cancer. METHODS: Patients with exocrine pancreatic cancer (n = 40), neuroendocrine cancer (n = 14), multiple endocrine neoplasia type 1 (n = 8), and chronic pancreatitis (n = 5) were studied. Other benign pancreatic diseases (n = 10) and specimens of normal pancreas (n = 7) were included as controls. Pancreatic tissue specimens were analyzed by Helicobacter-specific PCR-assay and products were characterized by denaturing gradient electrophoresis and DNA-sequencing. From a subset of the pancreatic cancer patients, gastric and/or duodenal tissue as well as gallbladder and ductus choledochus tissue were analyzed. Gallbladder and choledochus samples were included as controls. Stomach and duodenum samples were investigated to analyze whether a gastric helicobacter might disseminate to the pancreas in pancreatic cancer patients. Pancreatic specimens were analyzed by Bacteroides-specific PCR for detecting the translocation of indigenous gut microbes to the diseased pancreas. RESULTS: Helicobacter DNA was detected in pancreas (tumor and/or surrounding tissue) of 75% of patients with exocrine cancer, 57% of patients with neuroendocrine cancer, 38% of patients with multiple endocrine neoplasia, and 60% of patients with chronic pancreatitis. All samples from other benign pancreatic diseases and normal pancreas were negative. Thirty-three percent of the patients were helicobacter-positive in gastroduodenal specimens. Surprisingly, H. bilis was identified in 60% of the positive gastroduodenal samples. All gallbladder and ductus choledochus specimens were negative for helicobacter. Bacteroides PCR-assay was negative for all pancreatic samples. CONCLUSION: Helicobacter DNA commonly detected in pancreatic cancer suggests a possible role of the emerging pathogens in the development of chronic pancreatitis and pancreatic cancer.


Assuntos
Carcinoma Neuroendócrino/microbiologia , DNA Ribossômico/análise , Duodeno/química , Helicobacter/genética , Neoplasia Endócrina Múltipla Tipo 1/microbiologia , Pâncreas/química , Neoplasias Pancreáticas/microbiologia , Estômago/química , Adulto , Idoso , Bacteroides/genética , Bacteroides/fisiologia , Carcinoma Neuroendócrino/etiologia , Carcinoma Neuroendócrino/genética , Estudos de Casos e Controles , Ducto Colédoco/química , Ducto Colédoco/microbiologia , DNA Ribossômico/genética , Duodeno/microbiologia , Feminino , Vesícula Biliar/química , Vesícula Biliar/microbiologia , Helicobacter/fisiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/etiologia , Neoplasia Endócrina Múltipla Tipo 1/genética , Pâncreas/microbiologia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/genética , Reação em Cadeia da Polimerase , Estômago/microbiologia
9.
Ultrastruct Pathol ; 28(3): 171-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15471431

RESUMO

A granular cell tumor (GCT) in a 39-year-old white man is reported. It was localized in the intrapancreatic part of the common bile duct and caused obstruction of the bile downflow. The patient underwent radical surgical procedures because a malignant tumor was clinically suspected. Macroscopically, the tumor appeared as a duct stricture caused by diffuse infiltration of neoplastic cells in the walls. In the cytoplasm smaller and larger PAS-positive granules were present and constantly reactive to S-100 and NSE antibodies. Ultrastructurally, cytoplasmic granules appeared as membrane-bound vacuoles of variable size and shape containing debris, disrupted mitochondria, and myelin figures. No basal lamina around cell cytoplasm was observed. GCTs are relatively uncommon soft tissue tumors usually presenting in the skin and subcutaneous tissues or tongue. The prognosis in any location is quite good, but very rare malignant GCTs (1-2%) are documented. Complete excision reduces the risk of recurrence. Accurate operative diagnosis seems to be critical when the tumors are located in the intrapancreatic common bile duct as in this reported case. Gastro-pancreatico-duodenectomy is too radical a procedure for such a benign lesion and additional assessments and investigations are recommanded before such an extensive radical surgery.


Assuntos
Neoplasias do Ducto Colédoco/patologia , Ducto Colédoco/patologia , Tumor de Células Granulares/patologia , Adulto , Membrana Basal/ultraestrutura , Biomarcadores Tumorais/análise , Ducto Colédoco/química , Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/química , Neoplasias do Ducto Colédoco/cirurgia , Constrição Patológica/patologia , Constrição Patológica/cirurgia , Intervalo Livre de Doença , Gastrectomia , Tumor de Células Granulares/química , Tumor de Células Granulares/cirurgia , Humanos , Imuno-Histoquímica , Filamentos Intermediários/química , Filamentos Intermediários/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Pancreaticoduodenectomia , Proteína Estafilocócica A/análise , Resultado do Tratamento , Vimentina/análise
10.
Cancer ; 93(3): 229-35, 2001 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-11391612

RESUMO

BACKGROUND: Cytologic evaluation of common bile duct brushings has a low sensitivity for diagnosing malignancy because of scant cellularity, poor cellular preservation, or sampling errors occur. The aim of this study was to evaluate whether cytology combined with image analysis improves the diagnostic accuracy of bile duct brushing in comparison with cytology alone. METHODS: Forty-nine specimens of bile duct brushings obtained from 45 patients during endoscopic retrograde cholangiopancreatography were evaluated using cytology and image analysis. Specimens were classified as negative, atypical, suspicious, or malignant by using cytologic evaluation. DNA histograms were classified as diploid (D), broad diploid (BD), aneuploid (A), or tetraploid (T). Degree of hyperploidy (DH), representing cells with a DNA content > 5C was evaluated using a cutoff value of > or = 1%. Final diagnosis of cancer was based on tissue specimens that were obtained by fine-needle aspiration or surgical biopsy and clinical fol- low-up. RESULTS: Thirty-four patients ultimately proved to have a malignancy. Cytology revealed 19 negative cases, 15 atypical cases, 9 suspicious cases, and 6 malignant cases. Together, suspicious and malignant cytology cases yielded a sensitivity of 44% and a specificity of 100% for a cytologic diagnosis of cancer. The DNA histogram pattern was D in 24 cases, BD in 9 cases, and A in 16 cases. BD and A patterns were significantly associated with malignancy (P < 0.001). A DH > or = 1% was noted in 22 cases. DH alone had a sensitivity of 62% and a specificity of 91% and was significantly associated with malignancy (P < 0.004). Atypical cytology alone had a false-negative rate of 29%, but in combination with a DH > or = 1%, the false-negative rate decreased to 7%. Additionally, when the authors combined atypical, suspicious, and malignant cytology with a DH > or = 1%, the diagnostic sensitivity increased to 88%, but the specificity decreased to 73%. CONCLUSIONS: Combined cytology and image analysis of bile duct brushing increased diagnostic sensitivity compared with cytology alone. The findings suggest that image analysis may help select patients having atypical cytology who should undergo a more rigorous evaluation for malignancy. A larger prospective study of the usefulness of combined cytology and image analysis of bile duct brushing is warranted.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ducto Colédoco/patologia , DNA de Neoplasias/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/química , Colangiopancreatografia Retrógrada Endoscópica , Ducto Colédoco/química , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Ploidias , Sensibilidade e Especificidade
11.
Pediatr Surg Int ; 16(1-2): 26-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10663829

RESUMO

Pancreaticobiliary maljunction (PBM), a congenital anomaly, causes regurgitation of pancreatic juice into the biliary tract, where it exerts a hazardous influence. However, changes in the common bile duct (CBD) remain obscure due to a lack of suitable experimental models. Using cats, we have developed an experimental model of PBM without bile-duct dilatation that allows the pure effects of PBM to be studied. Histologic and cellular kinetic changes in the CBD were analyzed in 6 controls and 9 experimental animals that survived for more than 6 months. CBD sections were stained with hematoxylin and eosin and a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). Invaginations of the bile-duct epithelium or parietal sacculi increased, and peribiliary glands were well-developed. PCNA-positive cells significantly increased in the CBD, especially in the parietal sacculi and glands. It is concluded that PBM increases the cell cycle in CBD epithelium and subsequently developed peribiliary glands. These developed glands may be associated with the formation of protein plugs, often seen in patients with PBM.


Assuntos
Doenças Biliares/patologia , Ducto Colédoco/patologia , Pancreatopatias/patologia , Animais , Doenças Biliares/metabolismo , Gatos , Ducto Colédoco/química , Dilatação Patológica , Modelos Animais de Doenças , Epitélio/química , Epitélio/patologia , Imuno-Histoquímica , Pancreatopatias/metabolismo , Antígeno Nuclear de Célula em Proliferação/análise
12.
Naunyn Schmiedebergs Arch Pharmacol ; 360(3): 344-53, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10543438

RESUMO

In functional experiments, we have investigated the effect exerted by neurotransmitters released from capsaicin-sensitive primary afferent nerve terminals in the isolated guinea-pig common bile duct. In resting preparations, capsaicin (0.1 microM) produced a quick contraction (45.1+/-4% of KCl 80mM) which was abolished by either atropine (1 microM) or tetrodotoxin (0.5 microM). The tachykinin receptor-selective antagonists GR 82334 (NK1 receptor-selective; 3 microM), MEN 11420 (NK2 receptor-selective; 1 microM) and SR 142801 (NK3 receptor-selective; 0.1 microM) administered separately failed to reduce the capsaicin-evoked contraction, whereas any combination of the three antagonists was effective: GR 82334 plus MEN 11420, 36+/-7% reduction; GR 82334 plus SR 142801, 48+/-4% reduction; MEN 11420 plus SR 142801, 55+/-3% reduction; GR 82334 plus MEN 11420 plus SR 142801, 57+/-5% reduction. Neither the CGRP1 receptor antagonist h-CGRP (8-37) (1.5 microM) nor the P2X purinoceptor antagonist PPADS (50 microM) affected the contractile response to capsaicin. The effect of capsaicin (0.1 microM) was abolished by pretreatment with capsaicin itself (10 microM for 15 min). Human calcitonin gene-related peptide (h-CGRP; 0.1 microM) mimicked the effect of capsaicin on resting preparations (contractile response =28% of KCl 80 mM). In preparations precontracted with a submaximal concentration of KCl (24 mM), and in the presence of atropine (1 microM), GR 82334 (3 microM) and MEN 11420 (3 microM), capsaicin (1 microM) produced a tetrodotoxin-insensitive long-lasting relaxation (45+/-3% reduction of tone, at 4min from administration), which was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100 microM). h-CGRP (10-50 nM) produced a similar sustained relaxation of precontracted preparations (59+/-4% reduction of tone). h-CGRP (8-37) (1.5 microM) almost completely reversed the relaxations produced by both capsaicin and h-CGRP. Application of electrical field stimulation (EFS: trains of stimuli of 10Hz; 0.25ms pulse width; supramaximal voltage; for 60s) to precontracted preparations produced a sustained, tetrodotoxin (1 microM)-sensitive relaxation (32+/-4% reduction of tone). L-NOARG (100 microM) greatly reduced (69+/-5% inhibition) the EFS-elicited relaxation. A complete reversal of the relaxant response to EFS into a contraction was obtained by administering L-NOARG to preparations in which a functional blockade of capsaicin-sensitive primary afferent neurons had been achieved by incubating the tissue with capsaicin (10 microM) for 15 min. At immunohistochemistry, tachykinin- and CGRP-immunoreactivities (TK-IR/CGRP-IR) were detected in varicose nerve fibers throughout the common bile duct, while TK-IR cell bodies were observed in the terminal portion (ampulla) only. In vivo pretreatment with capsaicin (50 mg/kg; 6-7 days before) decreased the number of CGRP-IR nerves, whereas the TK-IR neural network was apparently unchanged. In conclusion, our data provide functional evidence for the presence of capsaicin-sensitive primary afferent nerve endings in the guinea-pig terminal biliary tract, whose stimulation by capsaicin or EFS produces the release of tachykinins and CGRP. In addition, morphological evidence is provided that the bulk of TK-IR material in the biliary tract is contained in intrinsic neuronal elements, while CGRP in this tissue is of extrinsic origin only. Tachykinins, probably released in small amounts by capsaicin, act by activating receptors of the NK1, NK2 and NK3 type, most probably located on intrinsic cholinergic neurons, which in turn release ACh to produce the final excitatory motor response. The contractile response to capsaicin obtained in the presence of the three tachykinin receptor antagonists could be due to the co-released CGRP and/or to other unknown neurotransmitters. CGRP produces either indirect excitatory or direct inhibitory responses by stimulation of CGRP2 and CGRP1 receptors, respectively.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Capsaicina/farmacologia , Ducto Colédoco/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Taquicininas/fisiologia , Animais , Atropina/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/análise , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Ducto Colédoco/química , Ducto Colédoco/fisiologia , Estimulação Elétrica , Cobaias , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Antagonistas dos Receptores de Neurocinina-1 , Fragmentos de Peptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Fisalemina/análogos & derivados , Fisalemina/farmacologia , Piperidinas/farmacologia , Cloreto de Potássio/farmacologia , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Receptores da Neurocinina-2/antagonistas & inibidores , Receptores da Neurocinina-3/antagonistas & inibidores , Receptores de Taquicininas/antagonistas & inibidores , Taquicininas/análise , Tetrodotoxina/farmacologia
13.
Virchows Arch ; 431(3): 219-24, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9334845

RESUMO

Inflammatory pseudotumour of the common bile duct (CBD) is extremely rare. A 58-year-old Japanese female without choledocolithiasis underwent pancreatico-duodenectomy for constriction of the middle lower region of the CBD. A submucosal tumour protruding into the CBD, was histologically inflammatory consisting of fibroblastic cells, collagen fibres and myxoid stroma with chronic inflammatory cells. This lesion was surrounded by an irregular fibrosclerosing lesion with obliterative phlebitis which involved the neighbouring pancreas and lymph nodes. Clonal analysis of the tumour by polymerase chain reaction analysis of X chromosome inactivation patterns, confirmed the polyclonal nature of the lesion. Immunohistochemically, the fibroblastic cells in both lesions had the same phenotype [vimentin (+), desmin (-), muscle-specific actin (-) and CD34 (+)] suggesting that these lesions with different histological features represent zonation of the same inflammatory process. The outer lesion extended irregularly into adjacent pancreatic tissue and lymph nodes. This fact made it difficult to differentiate this from a malignant lesion, even if frozen sections contained no atypical cells.


Assuntos
Doenças do Ducto Colédoco/patologia , Granuloma de Células Plasmáticas/patologia , Antígenos CD34/análise , Biomarcadores/análise , Ducto Colédoco/química , Doenças do Ducto Colédoco/genética , Mecanismo Genético de Compensação de Dose , Feminino , Granuloma de Células Plasmáticas/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
14.
Scand J Clin Lab Invest ; 57(4): 307-15, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9249878

RESUMO

beta-Glucuronidase of human or bacterial origin may deconjugate bilirubin diglucuronide, causing pigment gallstones. Intrinsic interference by biliary compounds must be minimized for accurate assay of beta-glucuronidase. We report a modified ion-pair extraction of interfering substances by tetrahexylammonium chloride (THAC) in ethyl acetate in the presence of albumin, and a microtitre plate assay for biliary beta-glucuronidase activity in bile with the substrate p-nitrophenol-glucuronide. Adding albumin improved the recovery of beta-glucuronidase activity to 99.8% (CV 1.9%), and 92.2% of the bilirubin in bile samples was extracted in one step. Competitive inhibition was overcome by increasing the substrate concentration. In endoscopically obtained common duct bile from 44 patients, five different beta-glucuronidase activity peaks were identified, at pH 3.9, 4.8, 5.3, 5.8 and 7.2. The pH profiles were classified into one bacterial pattern and five patterns for presumed human beta-glucuronidase. Of the latter patterns, four displayed dual activity peaks. In a second sample, obtained at follow up in four patients, their original pH profile was maintained. In conclusion, using the modified purification and assay system, we found functionally diverse subcategories of human beta-glucuronidase with respect to activity at variable pH. Our results indicate that several pH optima have to be taken into consideration in order to clarify the role of human biliary beta-glucuronidase in the pathogenesis of pigment gallstones. Bacterial beta-glucuronidase activity was associated with duodenal diverticula (p < 0.05) and common duct stones (p < 0.05).


Assuntos
Bile/enzimologia , Colelitíase/enzimologia , Ducto Colédoco/enzimologia , Glucuronidase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Bile/efeitos dos fármacos , Doenças dos Ductos Biliares/enzimologia , Colelitíase/patologia , Ducto Colédoco/química , Feminino , Glucuronidase/isolamento & purificação , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Compostos de Amônio Quaternário/farmacologia
15.
J Immunol ; 158(4): 1941-8, 1997 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9029136

RESUMO

The phenotype of T cells associated with the common bile duct (CBD) is unknown. We investigated the hypothesis that they behave like other intraepithelial lymphocytes (IEL). Thus, we sought to determine the phenotype, TCR repertoire, and epithelial recognition of T cells obtained during endoscopic retrograde cholangiopancreatography. Three subjects were studied: two with primary sclerosing cholangitis and one normal control. After establishing a short-term T cell line, cells were 1) stained with mAbs for flow cytometric analysis, 2) analyzed for TCRB chain transcript expression, and 3) used as effector cells for cytotoxicity and proliferation. Flow cytometry revealed that for all the subjects 98% of the T cells were TCR-alpha beta-positive. Immunohistology of the CBD showed that the epithelium and lamina propria contained significant numbers of CD3+ CD43+ CD45RO+ lymphocytes. Complementarity-determining region 3 length displays suggested that the CBD-derived lines were oligoclonal. This was confirmed by cloning and random sequencing of PCR amplification products using TCRBV region family-specific primers; TCRB chain sequences were reiterated in all transcripts analyzed. In one case, two expanded TCRB clones could be identified that were persistent in the bile duct over a 1-yr period. The CBD-derived lines were cytolytic in a redirected lysis assay and caused cytolysis of an intestinal epithelial cell line (Caco-2). This recognition was likely preferential for intestinal epithelial cells, since a CBD-derived line exhibited proliferation to two intestinal epithelial cell lines (HT-29 and Caco-2) but not three other lines (HepG2, human foreskin fibroblast, and KD). We conclude that the CBD contains IELs that share several characteristics with intestinal IELs.


Assuntos
Células Clonais/imunologia , Ducto Colédoco/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Células CACO-2 , Linhagem Celular , Células Clonais/química , Células Clonais/patologia , Ducto Colédoco/química , Ducto Colédoco/patologia , Citotoxicidade Imunológica , Epitélio/química , Epitélio/imunologia , Epitélio/patologia , Fibroblastos , Humanos , Imunofenotipagem , Fígado , Sarcoma de Mastócitos , Camundongos , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Análise de Sequência , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/patologia
16.
Scand J Clin Lab Invest ; 53(7): 757-63, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8272764

RESUMO

Bile protein assays are complicated due to interference by other bile substances. In the present study we describe a microtiter plate method for the purification and quantification of bile proteins. The method is based on addition of acetonitrile in three steps to reconstituted freeze-dried bile, followed by ethanol washing of the precipitated proteins. Finally, protein in the precipitate is quantitated by two-point colour development using micro BCA reagents. Overall recoveries of protein in reconstituted bile spiked with exogenous protein (Seronorm) ranged from 91.0% (coefficient of variation; CV = 7.0%) to 97.1% (CV = 2.4%) by recoveries of 125I-Fibrinogen and 125I-Albumin. Bile pigments were largely removed during precipitation and washing, as verified by high pressure liquid chromatography (HPLC). Preferably the samples should be freeze-dried initially, as this lowered the blank readings. Two-point colour development with the BCA reagents were identical for standards assayed directly and standards added to protein depleted bile, and processed through all steps. Hence, no interference by either residual bile constituents nor the reagents upon the BCA protein assay could be detected. Standard curves ranged from 0.05 to 5.0 gl-1 (r > 0.98). Within day reproducibility (n = 15) was 7.8% (CV) and day to day (n = 10) was 12.1% (CV). Mean protein concentration in common duct bile from 30 patients was 1.20 gl-1 (range 0.34-3.87 gl-1). The method appears suitable for assay of bile protein, requires only limited sample volumes and allows processing of many samples within a short time.


Assuntos
Acetonitrilas , Ducto Colédoco/química , Proteínas/análise , Quinolinas , Doenças Biliares/metabolismo , Precipitação Química , Humanos , Microquímica , Pancreatopatias/metabolismo
17.
Aust N Z J Surg ; 63(2): 109-12, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8297295

RESUMO

Since secondary bile acids have mutagenic potency and choledochal cyst patients with or without cyst-enterostomy have a high risk of developing bile duct carcinoma, we examined the hypothesis that secondary bile acids are elevated in the choledochal cyst and possibly cause biliary tract carcinoma. Eleven choledochal cyst patients with or without previous cyst-enterostomy or biliary tract carcinoma, seven patients with biliary tract carcinoma not associated with choledochal cyst and five patients with cholecystolithiasis were examined. Samples were directly needle aspirated from the cyst or by cannulating a tube into the common bile duct through the cystic duct. The concentrations of each bile acid in these samples were quantified by gas-liquid chromatography and compared. Neither the relative composition nor the absolute concentration of secondary bile acids (deoxycholic acid, lithocholic acid) elevated in patients with choledochal cyst compared with the values in the non-choledochal cyst patients with or without biliary tract carcinoma. The presence of biliary tract carcinoma or previous cyst-enterostomy did not affect the concentrations of secondary bile acids. The results suggest that the factor other than secondary bile acids can be primarily responsible for the high risk of bile duct carcinoma in patients with choledochal cyst.


Assuntos
Ácidos e Sais Biliares/análise , Neoplasias do Sistema Biliar/etiologia , Cisto do Colédoco/química , Adulto , Idoso , Análise de Variância , Cisto do Colédoco/complicações , Ducto Colédoco/química , Humanos , Pessoa de Meia-Idade , Fatores de Risco
18.
HPB Surg ; 1(1): 15-20, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2484792

RESUMO

We describe the histological and histochemical changes of the common bile-duct mucosa in specimens obtained by means of peroral cholangioscopy, 1-12 years after choledochoduodenal anastomosis. Our findings--hyperplasia of the superficial epithelium, metaplastic goblet cells containing predominantly acid sialomucins, and pyloric-like gland formation containing neutral mucins--express a morphological and functional differentiation of the common bile-duct mucosa that probably facilitates its survival in a different environment. We consider that these adaptive changes may explain the uneventful long-term postoperative period of choledochoduodenostomized patients.


Assuntos
Coledocostomia , Ducto Colédoco/patologia , Ducto Colédoco/química , Epitélio/patologia , Humanos , Mucinas/química , Mucosa/química , Mucosa/patologia , Sialomucinas , Coloração e Rotulagem
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