RESUMEN
BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) may cause excessive duodenogastric reflux (DGR) in a similar manner to distal gastrectomy, particularly after antral resections. We aimed to examine the occurrence of DGR after ESD. PATIENTS AND METHODS: Patients with gastric neoplasm for whom ESD was indicated were categorized according to lesion site: the antral group (lower [L] stomach, n = 46) and the nonantral group (upper or middle [U or M] stomach, n = 49). Endoscopy was performed before ESD, the day after ESD, and 3 months after ESD, and the fasting bile acid concentration (BAC) in the gastric juice was analyzed. RESULTS: BAC values showed significant interaction between time point and group, although this association differed in the antral and nonantral groups. BACs on the day after ESD were higher in the antral group than in the nonantral group, but not the pre-ESD and 3 months post-ESD levels. In the antral group only, fasting BACs increased significantly the day after ESD and decreased to baseline levels 3 months post-ESD. There was also a correlation between BAC and lesion location in the antral subgroups, with significantly higher BACs found the day after ESD in patients with lesser curvature lesions. CONCLUSIONS: ESD of lesions in the antral lesser curvature may lead to a transient early increase in DGR. However, ESD does not result in long-term DGR, a factor that is known to increase the risk of carcinogenesis following gastrectomy.
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Disección/efectos adversos , Reflujo Duodenogástrico/epidemiología , Reflujo Duodenogástrico/etiología , Mucosa Gástrica/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Ácidos y Sales Biliares/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND AND STUDY AIMS: Several studies have shown the value of capsule endoscopy and double balloon endoscopy (DBE) in small-intestinal bleeding. The purpose of this study was to evaluate the impact of capsule endoscopy results on subsequent DBE examination, and the 1-year clinical outcome of this combined approach in patients with obscure gastrointestinal bleeding (OGIB). PATIENTS AND METHODS: A total of 45 consecutive patients with OGIB underwent capsule endoscopy. Patients with positive capsule endoscopy results underwent DBE for biopsy or therapy, and those with negative results underwent further assessment for possible diagnostic misses on capsule endoscopy. Tumors, ulcerations, and vascular lesions were considered as sources of bleeding. Diagnoses of OGIB lesions and clinical outcome were assessed 1 year after these examinations. RESULTS: Responsible lesions were found in 22 patients (49 %): 19 lesions in 18/45 patients (40 %) undergoing capsule endoscopy, and 18/36 patients (50 %) undergoing subsequent DBE. In all, 10 tumors, nine vascular lesions, and four ulcerations were found. In two patients, vascular lesions were only later diagnosed by conventional methods (4 %). Capsule endoscopy results guided our choice of the proper DBE model for successful therapeutic intervention in five patients. Re-bleeding rates were low during 1-year follow-up of the entire group (mean follow-up, 18.8 months): 5 % in cases with positive diagnoses on capsule endoscopy and/or DBE, and 12 % in negative cases. CONCLUSIONS: A combined approach using capsule endoscopy followed by DBE proves valuable in the diagnosis and treatment of patients with OGIB, leaves a low rate of undiagnosed bleeding sources, and has a good long-term outcome.
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Endoscopios en Cápsulas , Endoscopía Capsular/métodos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Intestino Delgado/patología , Adulto , Anciano , Anciano de 80 o más Años , Oclusión con Balón/métodos , Estudios de Cohortes , Terapia Combinada , Endoscopía Gastrointestinal/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/metabolismo , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/metabolismo , Acromegalia , Adulto , Hormona de Crecimiento Humana/sangre , Humanos , Hiperplasia , Hipertiroidismo/complicaciones , Hipertiroidismo/patología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Imagen por Resonancia Magnética , Masculino , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico por imagen , Neoplasia Endocrina Múltiple Tipo 1/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Enfermedades de la Hipófisis/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.
Asunto(s)
Adenoma/metabolismo , Quimiocina CCL2/metabolismo , Neoplasias Colorrectales/metabolismo , Ciclooxigenasa 2/metabolismo , Macrófagos/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Celecoxib , Células Cultivadas , Quimiocina CCL2/antagonistas & inhibidores , Quimiocina CCL2/farmacología , Quimiocinas/metabolismo , Ciclooxigenasa 1/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Dinoprostona/metabolismo , Dinoprostona/farmacología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Macrófagos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Pirazoles/farmacología , Sulfonamidas/farmacología , Técnicas de Cultivo de Tejidos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.
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Antiinflamatorios no Esteroideos/efectos adversos , Antiulcerosos/uso terapéutico , Famotidina/uso terapéutico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Omeprazol/análogos & derivados , Omeprazol/uso terapéutico , Úlcera Péptica/prevención & control , 2-Piridinilmetilsulfinilbencimidazoles , Anciano , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Lansoprazol , Masculino , Persona de Mediana Edad , Úlcera Péptica/inducido químicamente , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Helicobacter pylori eradication decreases recurrence of peptic ulcers with marked improvement in histological inflammation, but gastric mucosal injuries may be developed even after eradication. PURPOSE: To investigate the mechanisms responsible for the development of gastric erosions after eradication, we analysed the relationship between clinicopathological risk factors and the occurrence of gastric erosion after curing H. pylori infection. PATIENTS: Sixty patients underwent endoscopy before, and 3, 6 and 12 months after the completion of H. pylori eradication. METHODS: Risk factors associated with the development of gastric erosions after eradication were assessed by multivariate analysis, and cyclooxygenase-1 and -2 immunoreactivity was histologically examined in the gastric mucosa before and after eradication. RESULTS: The cumulative prevalence of gastric erosions after H. pylori eradication was 38.3% within 1 year. Using multivariate analysis, corpus gastritis scores (inflammation score+activity score), corpus atrophy scores and an age of more than 50 years were found to be independent factors associated with the development of gastric erosion after eradication with odds ratios of 7.39, 0.13 and 5.00, respectively. Cyclooxygenase-2 immunoreactivity of the corpus was decreased for the non-erosion group after eradication, but not for the erosion group. CONCLUSIONS: Severe gastritis or less severe atrophy in oxyntic glands but not in pyloric glands before eradication may be involved in the development of gastric erosions after curing H. pylori infection.
Asunto(s)
Mucosa Gástrica/patología , Gastritis/patología , Infecciones por Helicobacter/tratamiento farmacológico , Prostaglandina-Endoperóxido Sintasas/metabolismo , Factores de Edad , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Atrofia , Ciclooxigenasa 1 , Quimioterapia Combinada , Femenino , Mucosa Gástrica/enzimología , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Gastroscopía , Helicobacter pylori , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Análisis Multivariante , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/microbiología , Factores de RiesgoRESUMEN
BACKGROUND: and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation. METHODS: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry. RESULTS: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related. CONCLUSIONS: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.
Asunto(s)
Quimiocina CCL2/fisiología , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/inmunología , Helicobacter pylori/fisiología , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Linfocitos T/metabolismo , Western Blotting , Ciclooxigenasa 2 , Citocinas/inmunología , Activación Enzimática , Ensayo de Inmunoadsorción Enzimática , Mucosa Gástrica/inmunología , Gastritis/inmunología , Gastritis/microbiología , Helicobacter pylori/inmunología , Humanos , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Células Jurkat/metabolismo , Células Jurkat/microbiología , Activación de Linfocitos , Proteínas de la Membrana , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/microbiologíaRESUMEN
BACKGROUND: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. METHODS: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. RESULTS: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. CONCLUSIONS: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.
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Adenoma/sangre , Adenoma/epidemiología , Consumo de Bebidas Alcohólicas/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/epidemiología , Lípidos/sangre , Adenocarcinoma/sangre , Adenocarcinoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/fisiopatología , Colesterol/sangre , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Triglicéridos/sangreRESUMEN
BACKGROUND: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. AIM: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. METHODS: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. RESULTS: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. CONCLUSIONS: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.
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Ácido Gástrico/metabolismo , Gastritis/etiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Úlcera Péptica/etiología , Biopsia , Endoscopía Gastrointestinal , Femenino , Mucosa Gástrica/patología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial. AIM: To examine the effect of the interaction between H. pylori and non-steroidal anti-inflammatory drugs on gastric mucosal injury. METHODS: Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo-oxygenase proteins were determined by Western blot analysis and cyclo-oxygenase activity. RESULTS: A 2-day course of indometacin did not cause an increase in gastric damage in H. pylori-infected Mongolian gerbils compared to uninfected gerbils, while a 7-day course of indometacin caused additive gastric damage in H. pylori-infected animals. H. pylori infection induced cyclo-oxygenase-2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo-oxygenase activity in H. pylori-infected animals, while treatment for 7 days inhibited both cyclo-oxygenase-1 and cyclo-oxygenase-2 activities. Pre-treatment with a selective cyclo-oxygenase-2 inhibitor aggravated mucosal injury in H. pylori-infected animals treated or not treated with indometacin for 2 days. CONCLUSIONS: Our results suggest that cyclo-oxygenase-2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non-steroidal anti-inflammatory drugs. Therefore, inhibition of cyclo-oxygenase-2 activity may enhance non-steroidal anti-inflammatory drug-caused gastric damage in H. pylori-infected animals.
Asunto(s)
Antiinflamatorios no Esteroideos/toxicidad , Inhibidores de la Ciclooxigenasa/toxicidad , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Indometacina/toxicidad , Isoenzimas/antagonistas & inhibidores , Úlcera Gástrica/etiología , Animales , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/enzimología , Gerbillinae , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/patología , Masculino , Úlcera Péptica Hemorrágica/etiología , Úlcera Péptica Hemorrágica/metabolismo , Úlcera Péptica Hemorrágica/patología , Peroxidasa/metabolismo , Prostaglandina-Endoperóxido Sintasas , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologíaRESUMEN
BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/epidemiología , Enfermedades Hematológicas/complicaciones , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We describe the lesions of extrapulmonary lymphangioleiomyomatosis (LAM) affecting the lymph nodes of the mediastinum and retroperitoneum in 22 women (mean age +/- SD, 42.4+/-10.5 years). In most of these patients, the diagnosis of extrapulmonary LAM preceded that of pulmonary LAM, usually by 1 to 2 years. Eleven patients had distinct symptoms, including chylous pleural effusion and/or ascites, abdominal pain, and palpable abdominal masses. In the other 11 patients, the masses caused no symptoms. Well-circumscribed, encapsulated masses, measuring up to 20 cm in size, occurred in the mediastinum in 2 patients, the upper retroperitoneum in 15, extensive areas of the retroperitoneum in 2, and the pelvis in 3. The masses exceeding 3 cm in diameter contained large, multiple cysts filled with yellow-tan chylous fluid. Histologically, the masses were characterized by a proliferation of smooth muscle cells (LAM cells) arranged in fascicular, trabecular, and papillary patterns, which were associated with slit-like vascular channels. The LAM cells varied from small, spindle-shaped cells to large epithelioid cells. Immunohistochemical studies showed a strong reactivity of most LAM cells for alpha-smooth muscle actin and smooth muscle myosin heavy chain and a weak to moderate reactivity of a lesser number of cells for desmin and nonmuscle myosin heavy chain II-B. A reaction for HMB-45 and estrogen and progesterone receptors was observed mainly in epithelioid LAM cells. These patterns of reactivity are similar to those observed in pulmonary LAM. However, the chylous cysts are not a feature of pulmonary LAM and are thought to result from obstruction of lymphatics.
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Linfangioleiomiomatosis/patología , Actinas/análisis , Adulto , Anciano , Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Femenino , Humanos , Antígenos Específicos del Melanoma , Persona de Mediana Edad , Cadenas Pesadas de Miosina/análisis , Proteínas de Neoplasias/análisisRESUMEN
A review is presented of the clinical and morphological manifestations of lymphangioleiomyomatosis (LAM), a systemic disorder of unknown etiology that affects women. The clinical features include dyspnea, hemoptysis, recurrent pneumothorax, chylothorax, and chylous ascites. It is characterized by: 1) proliferation of abnormal smooth muscle cells (LAM cells) in pulmonary interstitium and along the axial lymphatics of the thorax and abdomen; 2) thin-walled pulmonary cysts, and 3) a high incidence of angiomyolipomas. The pulmonary cystic lesions have a characteristic appearance on high resolution computed tomography. The most specific method for diagnosing LAM is lung biopsy to demonstrate the presence of LAM cells, either by their characteristic histological appearance or by specific immunostaining with HMB-45 antibody. LAM cells differ in several important respects from the types of smooth muscle cells normally present in lung. Their reactivity with HMB-45 antibody is localized in stage I and stage II melanosomes. LAM cells show additional evidence of incomplete melanogenesis, and the significance of these observations remains to be determined. Two types of LAM cells are recognized: 1) small, spindle-shaped cells that are centrally located in the LAM nodules and are highly immunoreactive for matrix metalloproteinase-2 (MMP-2), its activating enzyme (MT-1-MMP), and proliferating cell nuclear antigen (PCNA), and 2) large, epithelioid cells that are distributed along the periphery of the nodules and show a high degree of immunoreactivity with HMB-45 antibody and with antibodies against estrogen and progesterone receptors. Types of treatment used for LAM include oophorectomy, administration of Lupron or progesterone and in very severe cases, pulmonary transplantation (following the onset of respiratory insufficiency, not relieved by O(2)).
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Neoplasias Pulmonares/patología , Linfangioleiomiomatosis/patología , Anticuerpos Antineoplásicos/análisis , Antígenos de Neoplasias , Biomarcadores de Tumor/análisis , Femenino , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Linfangioleiomiomatosis/diagnóstico , Antígenos Específicos del Melanoma , Proteínas de Neoplasias/inmunologíaRESUMEN
BACKGROUND: Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. AIMS: To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. PATIENTS AND METHODS: Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n = 9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n = 45) and H pylori negative healthy subjects (n = 15). COX expression was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. RESULTS: COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. CONCLUSIONS: Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process.
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Gastritis/enzimología , Infecciones por Helicobacter , Helicobacter pylori/enzimología , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Úlcera Gástrica/enzimología , Adulto , Anciano , Western Blotting , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Femenino , Gastritis/microbiología , Infecciones por Helicobacter/enzimología , Humanos , Inmunohistoquímica , Masculino , Proteínas de la Membrana , Microscopía Electrónica , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
BACKGROUND: Increasing evidence suggests that mesothelial cells contribute to the control of inflammation in the peritoneal cavity by secreting prostaglandins. A study has shown that cyclooxygenase (COX)-2 knockout mice die partly as a result of peritonitis. AIM: To investigate the expression and location of COX in peritonitis associated with peptic ulcer perforation. METHODS: Gastric and duodenal tissues were collected intraoperatively from nine and four patients, respectively, and immunohistochemical staining for COX-1 and COX-2 was performed. RESULTS: Histologically, all patients had severe peritonitis around the perforation sites, into which many inflammatory cells and fibroblasts had infiltrated, and reactive mesothelial cells exhibited hyperplastic change. The COX-1 protein was not detected, whereas COX-2 was abundant in reactive mesothelial cells near the perforation site and disappeared away from the site. Macrophages and fibroblasts around the perforation site also revealed immunostaining for COX-2. CONCLUSIONS: Our results showed that COX-2 protein is induced in mesothelial cells, as well as in macrophages and fibroblasts, in inflamed peritoneal tissues associated with peptic ulcer perforation, suggesting involvement of COX-2 in tissue repair.
Asunto(s)
Perforación Intestinal/complicaciones , Isoenzimas/metabolismo , Úlcera Péptica/complicaciones , Peritonitis/etiología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Adulto , Anciano , Ciclooxigenasa 2 , Inducción Enzimática , Epitelio/enzimología , Femenino , Fibroblastos , Humanos , Inmunohistoquímica , Inflamación , Macrófagos , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Peritonitis/enzimologíaRESUMEN
OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.
Asunto(s)
Adenoma/diagnóstico , Neoplasias Colorrectales/diagnóstico , Índices de Eritrocitos , Adenoma/sangre , Adenoma/etiología , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Alcoholismo/sangre , Alcoholismo/diagnóstico , Colonoscopía , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/etiología , Deficiencia de Ácido Fólico/sangre , Deficiencia de Ácido Fólico/complicaciones , Deficiencia de Ácido Fólico/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: Heregulins (HRGs) regulate the proliferation and differentiation of various cell types. However, very little is known about their function in the gastrointestinal tract. The aim of this study was to investigate the role of HRGs on gastrointestinal cells. METHODS: We examined the expression of erbB receptors and HRG-alpha in human gastric cancer cell lines, rat gastrointestinal epithelial cells, and human gastric fibroblasts by Western blot analysis or reverse-transcription polymerase chain reaction. Receptor phosphorylation and heterodimerization induced by HRG-alpha were detected by Western blot analysis. We also evaluated the in vitro effects of HRG-alpha on cell proliferation and restitution. RESULTS: Cancer cell lines and rat epithelial cells expressed erbB2 and erbB3, but protein expression of erbB4 was not detected. HRG-alpha was detected only in gastric fibroblasts. HRG-alpha activated tyrosine phosphorylation of epidermal growth factor receptor (EGFR), erbB2, and erbB3 and induced not only erbB3/erbB2 but also erbB3/EGFR and erbB2/EGFR heterodimer formation in MKN-28 cancer cells. Simultaneous cultivation of MKN-28 cells with gastric fibroblasts resulted in tyrosine phosphorylation of erbB3 in MKN-28 cells. HRG-alpha also stimulated proliferation of MKN-28 cells and gastric epithelial cells. CONCLUSIONS: The data suggest that HRG-alpha may affect epithelial cell proliferation through mesenchymal-epithelial interaction in the gastric mucosa.
Asunto(s)
Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Neurregulina-1/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Animales , Células CHO , División Celular/fisiología , Cricetinae , ADN/biosíntesis , Sistema Digestivo/citología , Sistema Digestivo/metabolismo , Dimerización , Fibroblastos/metabolismo , Mucosa Gástrica/efectos de los fármacos , Humanos , Ligandos , Neurregulina-1/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Ratas , Receptor ErbB-2/química , Receptor ErbB-2/efectos de los fármacos , Receptor ErbB-3/química , Receptor ErbB-3/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Estómago/citología , Células Tumorales Cultivadas , Tirosina/metabolismoRESUMEN
BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of gastrointestinal ulcer and cancer along with tissue inhibitors of metalloproteinases (TIMPs). The purpose of this study is to examine their localization and functions in the normal stomach. METHODS: We examined the localization of MMP-1, MMP-2, MMP-9 and TIMP-2 in normal human and rabbit stomachs by light- and electron-microscopic immunohistochemistry and Western blotting, and the enzymatic activities of MMP-2 and MMP-9 by gelatin zymography. RESULTS: Immunohistochemistry revealed their localization in parietal cells, and surface and foveolar epithelial cells. Electron-microscopic immunohistochemistry of parietal cells showed immunolabeling of MMP-2 and TIMP-2 in the cisternae of the rough endoplasmic reticulum, and that of MMP-1 and MMP-9 in tubular structures in their cytoplasm. Western blotting revealed that the densities of MMP-2 and MMP-9 bands were higher for the fundic gland region than for the pyloric gland region. Gelatin zymography revealed that tissue extracts of the fundic gland region exhibited higher enzymatic activity of MMP-2 and MMP-9 than those of the pyloric gland region. CONCLUSION: Normal rabbit and human stomachs contain MMP-1, MMP-2, MMP-9, and TIMP-2 and these are mainly localized in, and synthesized by parietal cells.
Asunto(s)
Colagenasas/análisis , Gelatinasas/análisis , Metaloendopeptidasas/análisis , Estómago/enzimología , Inhibidor Tisular de Metaloproteinasa-2/análisis , Adulto , Animales , Western Blotting , Femenino , Fibroblastos/enzimología , Fibroblastos/ultraestructura , Gelatina , Humanos , Técnicas para Inmunoenzimas , Masculino , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Músculo Liso/enzimología , Músculo Liso/ultraestructura , Células Parietales Gástricas/enzimología , Células Parietales Gástricas/ultraestructura , Conejos , Estómago/ultraestructuraAsunto(s)
Enfermedades del Colon/complicaciones , Enfermedades del Íleon/complicaciones , Válvula Ileocecal , Intususcepción/etiología , Lipomatosis/complicaciones , Anciano , Anastomosis Quirúrgica , Colon/diagnóstico por imagen , Colon/patología , Colon/cirugía , Enfermedades del Colon/diagnóstico , Enfermedades del Colon/cirugía , Colonoscopía , Estudios de Seguimiento , Humanos , Enfermedades del Íleon/diagnóstico , Enfermedades del Íleon/etiología , Enfermedades del Íleon/cirugía , Válvula Ileocecal/diagnóstico por imagen , Válvula Ileocecal/patología , Válvula Ileocecal/cirugía , Íleon/diagnóstico por imagen , Íleon/patología , Íleon/cirugía , Intususcepción/diagnóstico , Intususcepción/cirugía , Laparotomía , Lipomatosis/diagnóstico , Lipomatosis/cirugía , Masculino , Radiografía AbdominalRESUMEN
There have been only a few endoscopic studies with respect to lower intestinal lesions of leukaemia and malignant lymphoma, although there have been many autopsy studies of these lesions. The aim of this study was to clarify these lesions using endoscopy. Colonoscopy was performed on 11 of 341 patients with leukaemia and on 32 of 105 patients with malignant lymphoma for frequent diarrhoea, anal bleeding or abnormal findings on barium enema examination, between April 1984 and September 1994. In eight of the 11 patients with leukaemia on whom endoscopy was performed, nine lesions were found; aphthoid ulcers, small ulcers or large tumours due to leukaemic infiltration were found in five, and colorectal adenoma was found in only one patient. Antibiotic-associated haemorrhagic colitis or pseudomembranous colitis was found in one patient each. In 10 of the 32 patients with malignant lymphoma, 11 lesions were found. The following were found in one patient each: large lymphomatous tumours, a large lymphomatous ulcer, multiple small polypoid lesions, multiple lymphomatous polyposis; and colorectal cancer or adenoma in six patients. However, the autopsy findings in patients with both diseases were mostly pseudomembrane formation or ulcers due to fungal and/or bacterial infection. It is concluded that accurate endoscopic diagnosis of lower intestinal lesions in patients with leukaemia or malignant lymphoma is essential for staging and treatment of these diseases and for determining their prognosis. Most lesions in leukaemia are aphthoid and small ulcers are due to leukaemic infiltration or antibiotics; most lesions in malignant lymphoma are elevated lesions such as cancer, adenoma or lymphomatous lesions as determined by endoscopy. This is in contrast to pseudomembrane formation or ulcers due to fungal and/or bacterial infection which are detected at autopsy.