RESUMO
A 64-year-old man with essential thrombocythemia was admitted to our hospital because of cardiac failure. Echocardiography revealed severe mitral regurgitation and a gallbladder tumor was detected incidentally by ultrasonography. Although the gallbladder tumor was strongly suspected to be malignant, we considered that the radical operation would be possible because of its early stage. After treatment of cardiac failure, cholecystectomy was performed. Pathological examination proved that the gallbladder tumor was malignant in T1N0M0 stage I. Afterwards, mitral valve plasty and maze operation were performed concomitantly. During the operation, activated coagulation time was kept over 400 sec with heparin. The operation was completed without major problems and the postoperative course was uneventful. The patient has not suffered from the recurrence of a gallbladder carcinoma or mitral regurgitation for 2 years.
Assuntos
Neoplasias da Vesícula Biliar/complicações , Insuficiência da Valva Mitral/complicações , Trombocitemia Essencial/etiologia , Colecistectomia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/cirurgiaRESUMO
PURPOSE: Long-standing ulcerative colitis (UC) predisposes patients to the development of colorectal cancer, but surveillance of colitis-associated cancer by detecting the precancerous lesion dysplasia is often difficult because of its rare occurrence and normal-looking appearance. In sporadic colorectal cancer, aberrant crypt foci (ACF) have been reported by many investigators to be precursor lesions of the adenoma-carcinoma sequence. In the present study, we analyzed the genetic background of ACF to determine whether they could be precursors for dysplasia, and we examined the usefulness of endoscopic examination of ACF as a surrogate marker for surveillance of colitis-associated cancer. EXPERIMENTAL DESIGN: ACF were examined in 28 UC patients (19 patients with UC alone and 9 patients with UC and dysplasia; 2 of those patients with dysplasia also had cancer) using magnifying endoscopy. K-ras, APC, and p53 mutations were analyzed by two-step PCR RFLP, in vitro--synthesized protein assay, and single-strand conformation polymorphism, respectively. Methylation of p16 was analyzed by methylation-specific PCR. RESULTS: ACF that appeared distinct endoscopically and histologically were identified in 27 out of 28 UC patients. They were negative for K-ras, APC, and p53 mutations but were frequently positive for p16 methylation (8 of 11; 73%). In dysplasia, K-ras and APC mutations were negative but p53 mutation (3 of 5; 60%) and p16 methylation (3 of 5; 60%) were positive. There was a significant stepwise increase in the number of ACF from patients with UC alone to patients with dysplasia and to patients with cancer. Univariate and multivariate analyses showed significant correlations between ACF and dysplasia. CONCLUSIONS: We have disclosed an ACF-dysplasia-cancer sequence in colitis-associated carcinogenesis similar to the ACF-adenoma-carcinoma sequence in sporadic colon carcinogenesis. This study suggests the use of ACF instead of dysplasia for the surveillance of colitis cancer and warrants further evaluation of ACF as a surveillance marker in large-scale studies.
Assuntos
Colite Ulcerativa/patologia , Neoplasias Colorretais/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Progressão da Doença , Endoscopia Gastrointestinal , Feminino , Genes APC , Genes p16 , Genes p53 , Genes ras , Humanos , Masculino , Mutação , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , Lesões Pré-Cancerosas/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A 49-year-old man was admitted with high-grade fever, night sweating and cervical lymphadenopathy in September 2005. On examination, both neutrophilia and thrombocytosis were noted in the peripheral blood, a bone marrow examination revealed marked both myeloid and megakaryocytic hyperplasia. The sera obtained at initial presentation showed an elevated levels of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6). A pathologic diagnosis of T-cell rich B-cell lymphoma was made based on an inguinal lymph node biopsy. Following treatment with CHOP accompanied by rituximab (R-CHOP), both the neutrophilia and thrombocytosis subsided after 3 courses of R-CHOP, resulting in a complete remission after 4 courses of chemotherapy. Neutrophilia, thrombocytosis and T-cell rich B-cell lymphoma in this patient were considerably ameliorated with chemotherapy. We report here a patient with T-cell rich B-cell lymphoma associated with both neutrophilia and thrombocytosis, suggesting that the lymphoma triggered both myeloid and megakaryocytic hyperplasia.
Assuntos
Leucocitose/etiologia , Linfoma de Células B/complicações , Neutrófilos , Linfócitos T , Trombocitose/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Hiperplasia , Interleucina-6/sangue , Contagem de Linfócitos , Linfoma de Células B/diagnóstico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Células Mieloides/patologia , Resultado do TratamentoRESUMO
A 75-year-old man was admitted to our hospital in October, 2005 for examination of pre-diagnosed pancytopenia. His bone marrow showed myeloid dysplasia, and 30.4% of the nucleated cells were blasts. Our diagnosis was acute myelogenous leukemia with multilineage myelodysplasia (AML with MLD; WHO classification). A direct Coombs test proved positive, and the platelet-associated IgG (PA-IgG) level was elevated. After treatment with CAG (Ara-C + ACR + G-CSF), complete remission was obtained, showing negative on the direct Coombs test with PA-IgG levels returned to normal. The patient subsequently relapsed, testing positive on the direct Coombs test and experiencing a re-elevation of PA-IgG levels. We report here a first case of AML with MLD, direct Coombs test and PA-IgG assay.
Assuntos
Plaquetas/imunologia , Teste de Coombs , Imunoglobulina G/sangue , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Aclarubicina/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/tratamento farmacológico , Pancitopenia/etiologia , Prednisolona/administração & dosagem , Resultado do TratamentoRESUMO
Colorectal cancer is a disease with a high mortality rate and it has been increasing in prevalence worldwide. Chemoprevention, as well as primary and secondary prevention, for colorectal cancer have attracted much attention. Many chemopreventive trials have been performed, and several agents, including nonsteroidal antiinflammatory drugs, such as aspirin and sulindac, cyclooxygenase-2 selective inhibitors, such as celecoxib, vitamin D, folate, and calcium, have been shown to have some effect. In these chemopreventive trials, the targeted lesions used for evaluation were mainly polyps. However, the chemopreventive effects of some agents on polyps may require several years to evaluate. Further, larger polyps may not be susceptible to chemopreventive agents. Aberrant crypt foci (ACF) are tiny lesions at the earliest stage of colorectal carcinogenesis, which consist of large, thick crypts identified by dense, methylene blue staining. We succeeded in identifying human ACF in situ using magnifying endoscopy and found that the number of ACF, particularly dysplastic ACF, increased significantly from normal subjects to adenoma patients and then to cancer patients. We also found that the number, size, and dysplastic features of ACF are significantly correlated with the number of adenomas in adenoma patients. Thus, it was surmised that ACF are precursor lesions of the adenoma-carcinoma sequence in humans and that ACF may be the most appropriate lesions as targets for chemoprevention. We have shown that the number of ACF was significantly reduced in patients treated with sulindac. We are currently proceeding with a randomized, double-blind, chemopreventive trial targeting ACF.
Assuntos
Quimioprevenção , Neoplasias Colorretais/prevenção & controle , Animais , Ensaios Clínicos como Assunto , Glutationa S-Transferase pi , Glutationa Transferase/antagonistas & inibidores , Glutationa Transferase/metabolismo , Humanos , Pólipos Intestinais/tratamento farmacológico , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Camundongos , Lesões Pré-Cancerosas/tratamento farmacológicoRESUMO
PURPOSE: The aim of this study was to clarify the indications for a new endoscopic mucosal resection (EMR) technique that employs a cavitational ultrasonic surgical aspirator (CUSA). Endoscopic mucosal resection has proved an effective technique for treating early mucosal gastrointestinal cancer. However, resecting a lesion larger than 2 cm en bloc requires special devices and a long processing time; and it engenders the risk of bleeding, perforation, and other complications. METHODS: We investigated application of the CUSA for detaching the mucosa from the muscularis propria of extracted porcine stomachs and then clarified the specification of an endoscopic ultrasonic scalpel for endoscopic mucosal resection by investigating characteristics of two original, handmade prototype cavitational ultrasonic surgical aspirators. RESULTS: Use of a cavitational ultrasonic surgical aspirator should improve the ease and safety of detaching the mucosa. A small, high-power ultrasonic cylindrical vibrator should be developed to make possible a probe-type scalpel with a piezoelectric vibrator mounted in the tip of a catheter. An ultrasonic transmission-type scalpel could lead to the development of a new endoscopic mucosal resection device for clinical use. CONCLUSIONS: The CUSA should enable us to develop a safer, simpler, time-saving scalpel for endoscopic mucosal resection, although some resolvable technical problems remain. The CUSA might enable us to diagnose carcinoma invasion into the submucosa in aspirated specimens and then aspirate out the entire invading submucosal carcinoma.
Assuntos
Síndrome Hipereosinofílica/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Linfócitos T/patologia , Fatores de Poliadenilação e Clivagem de mRNA/genética , Idoso , Benzamidas , Células Clonais , Humanos , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/patologia , Mesilato de Imatinib , MasculinoAssuntos
Febre/etiologia , Pólipos/complicações , Gastropatias/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cholangiocarcinoma is markedly resistant to chemotherapy and has a dismal prognosis, but its mechanism of drug resistance is unknown. This study examines whether glutathione S-transferase-pi (GSTP1-1) is involved in resistance to anticancer drugs in cholangiocarcinoma and whether GSTP1-1-specific inhibitors can overcome this resistance. First, immunohistochemical examination disclosed strong staining of all our 17 cholangiocarcinoma specimens for GSTP1-1, irrespective of histological type. Transfection of the GSTP1-1 antisense expression vector into a human cholangiocarcinoma cell line (HuCCT1) apparently decreased its intracellular GSTP1-1 concentration, and the sensitivity of transfectants to adriamycin (ADR), cisplatin, and alkylating agents such as melphalan and 4-hydroxyperoxycyclophosphamide (4-HC) was increased significantly, compared with that of mock transfectants. We next synthesized GSTP1-1-specific inhibitors by elongating the carbon chain of the ethylester at the N-terminal of gamma-glutamyl-S-benzylcysteinyl-phenylglycyl diethylester and performed a pharmacokinetic study on them. Of six GSTP1-1 inhibitors tested, O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-d-phenylglycine ethylester (C16C2) showed the smallest volume of central compartment and smallest volume of distribution at steady state and the second smallest clearance, being the most effective inhibitor in vivo. The IC50 value of ADR or 4-HC for HuCCT1 cells decreased greater by treatment with C16C2 in a dose-dependent manner, paralleling the decrease in GSTP1-1 activity, than that of ADR or 4-HC alone. The antitumor activity of ADR or cyclophosphamide was clearly enhanced by combination therapy with C16C2 in a xenograft model. In conclusion, our results demonstrated that GSTP1-1 is a resistance factor for anticancer drugs in cholangiocarcinoma and that C16C2, a GSTP1-1-specific inhibitor, is a potent agent against the resistance.
Assuntos
Antineoplásicos/farmacologia , Colangiocarcinoma/patologia , Resistência a Múltiplos Medicamentos , Glutationa Transferase/antagonistas & inibidores , Isoenzimas/antagonistas & inibidores , Oligopeptídeos/farmacologia , Animais , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa S-Transferase pi , Humanos , Imuno-Histoquímica , Concentração Inibidora 50 , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/prevenção & controle , Oligopeptídeos/uso terapêutico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND & AIMS: Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for glutathione-S-transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of glutathione-S-transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. METHODS: Glutathione-S-transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to glutathione-S-transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to glutathione-S-transferase P1-1 was determined by inhibition assay of glutathione-S-transferase P1-1 activity. RESULTS: Aberrant crypt foci showed positive immunostaining for glutathione-S-transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the glutathione-S-transferase P1-1-specific inhibitor gamma-glutamyl-S-(benzyl)cysteinyl-R-phenylglycine diethylester. By transfection of glutathione-S-transferase P1-1, M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of glutathione-S-transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to glutathione-S-transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2-3 months. CONCLUSIONS: Glutathione-S-transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.