Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
Ann Oncol ; 29(4): 931-937, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365058

RESUMO

Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. Patients and methods: In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Results: Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13 €, P < 0.033). Conclusion: 18FDG-PET/CT, when added every 6 months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect. ClinicalTrials.gov identifier: NCT00624260.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Fluordesoxiglucose F18/administração & dosagem , Monitorização Fisiológica/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Custos e Análise de Custo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/economia
2.
Ann Oncol ; 27(1): 121-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26487578

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Resultado do Tratamento
3.
Aliment Pharmacol Ther ; 39(6): 619-28, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24467480

RESUMO

BACKGROUND: There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. AIM: To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. METHODS: In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). RESULTS: After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P < 0.001). No toxicity-related death was reported. CONCLUSIONS: The use of anti-cancer systemic therapy is safe and efficient in gastric MALT lymphoma. In this retrospective study, the combination of rituximab plus chlorambucil seems more efficient than rituximab or alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intervalo Livre de Doença , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Rituximab , Neoplasias Gástricas/patologia , Resultado do Tratamento , Adulto Jovem
4.
Br J Cancer ; 109(12): 3057-66, 2013 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-24196786

RESUMO

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS: Expression of HER2, ß-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of ß-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/metabolismo , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Análise de Sobrevida
5.
Colorectal Dis ; 13(7): 768-73, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20394639

RESUMO

AIM: We analysed local cellular and humoral immunity factors in the anal mucosa in an attempt to explain how HIV infection increases the risk of anal cancer in HPV-infected patients. METHOD: HIV-positive cases and matched HIV-negative controls with more than one recurrence of condylomas were included in a prospective study following treatment of the initial lesions. Patients were followed every 3 to 6 months for the development of anal intraepithelial neoplasia (AIN3) and cancer for up to 60 months. Tissue CD1a(+), CD3(+), CD4(+), CD8(+) cells and mRNAs of selected cytokines and chemokines were quantified and compared in patients with or without AIN3 or cancer using morphometric or immunohistochemistry analysis and qRT-PCR. RESULTS: Sixty-six individuals (22 patients and 44 controls) were included. In the case group, CD1a(+) and CD3(+) cell counts were significantly lower in biopsies from AIN3 and cancer specimens compared with those from AIN 1-2 or normal biopsies (P < 0.0001). A CD1a(+) count of < 10/mm was predictive of AIN3 and cancer (Odds ratio = 9.4, 95% CI: 5.4-18.3, P < 0.0001). IL-8 and IL23 levels were significantly higher in cancer than in non-cancer tissues regardless of HIV status (P = 0.02). FoxP3 expression was significantly higher in HIV-infected cases than in controls with AIN3/cancer (P < 0.04). CONCLUSION: Depletion of CD1a(+) and CD3(+) cells and overexpression of FoxP3 in the anal mucosa appear likely to contribute to the risk of HPV-related anal cancer in HIV-infected patients. Furthermore, overexpression of IL-8 and IL-23 in the anal mucosa might be responsible for the development of this cancer regardless of HIV status.


Assuntos
Canal Anal/metabolismo , Neoplasias do Ânus/virologia , Carcinoma in Situ/virologia , Fatores de Transcrição Forkhead/metabolismo , Infecções por HIV/complicações , Infecções por Papillomavirus/complicações , Adulto , Canal Anal/imunologia , Antígenos CD1 , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/patologia , Complexo CD3 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Carcinoma in Situ/imunologia , Feminino , Infecções por HIV/imunologia , Humanos , Interleucina-23/metabolismo , Interleucina-8/metabolismo , Contagem de Linfócitos , Masculino , Infecções por Papillomavirus/imunologia , RNA Mensageiro/metabolismo , Análise de Regressão , Fatores de Risco
6.
Ann Oncol ; 21(9): 1786-1793, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20223786

RESUMO

BACKGROUND: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. PATIENTS AND METHODS: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. RESULTS: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. CONCLUSIONS: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Duodenais/tratamento farmacológico , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Jejuno/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Neoplasias Duodenais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Neoplasias do Íleo/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Irinotecano , Neoplasias do Jejuno/patologia , Leucovorina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Aliment Pharmacol Ther ; 30(4): 414-21, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19392867

RESUMO

BACKGROUND: Previous studies suggest a poor prognosis of epidermoid anal cancer in HIV+ patients. AIM: To investigate the long-term outcome of epidermoid anal cancer in HIV+ and HIV- patients in the highly active antiretroviral treatment (HAART) era. METHODS: We included all patients with epidermoid anal cancer referred to six hospitals from 1998 to 2004. RESULTS: In all, 151 patients (44 HIV+, 107 HIV-) were reviewed retrospectively for 27 (median of 16-44) months. HIV+ patients were male (100% vs. 27%, P < 0.001) and younger (45 vs. 62 years old, P < 0.001) than HIV- patients. No significant differences were observed in the tumour stage, pelvic radiotherapy dose or concomitant chemotherapy, according to the HIV status. After chemoradiotherapy, similar numbers of HIV+ and HIV- patients had grade III-IV toxicity. A complete response was obtained in 82% and 75% (N.S.) of cases, respectively. The disease-free survival rates were 77% and 67% (N.S.) and the overall survival rates were 85% and 84% (N.S.), respectively, after 3 years of follow-up. Duration of HIV infection, viral load and CD4 count had no effect on the survival rate of HIV+ patients with EAC. CONCLUSIONS: The clinical outcome of HIV+ patients with epidermoid anal cancer is similar to that of HIV- patients. Therefore, the same therapeutic guidelines should be applied to both populations.


Assuntos
Terapia Antirretroviral de Alta Atividade , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/complicações , Adulto , Fatores Etários , Idoso , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/virologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Feminino , Soropositividade para HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Estatística como Assunto , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento
8.
Br J Cancer ; 98(5): 875-80, 2008 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-18301402

RESUMO

We assessed the potential benefits of including systematic 18fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting tumour recurrence in a prospective randomised trial. Patients (N=130) who had undergone curative therapy were randomised to undergo either conventional (Con) or FDG-PET procedures during follow-up. The two groups were matched at baseline. Recurrence was confirmed histologically. 'Intention-to-treat' analysis revealed a recurrence in 46 patients (25 in the FDG-PET group, and 21 in the Con group; P=0.50), whereas per protocol analysis revealed a recurrence in 44 out of 125 patients (23 and 21, respectively; P=0.60). In another three cases, PET revealed unexpected tumours (one gastric GIST, two primary pulmonary cancers). Three false-positive cases of FDG-PET led to no beneficial procedures (two laparoscopies and one liver MRI that were normal). We failed to identify peritoneal carcinomatosis in two of the patients undergoing FDG-PET. The overall time in detecting a recurrence from the baseline was not significantly different in the two groups. However, recurrences were detected after a shorter time (12.1 vs 15.4 months; P=0.01) in the PET group, in which recurrences were also more frequently (10 vs two patients) cured by surgery (R0). Regular FDG-PET monitoring in the follow up of colorectal cancer patients may permit the earlier detection of recurrence, and influence therapy strategies.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Gut ; 57(6): 772-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17965063

RESUMO

BACKGROUND AND AIMS: Colorectal cancer (CRC) harbours different types of DNA alterations, including microsatellite instability (MSI). Cancers with high levels of MSI (MSI-H) are considered to have a good prognosis, probably related to lymphocyte infiltration within tumours. The aim of the present study was to characterise the intratumoural expression of markers associated with the antitumour immune response in mismatch repair (MMR)-proficient (MSS) colon cancers. METHODS: Ninety human colon cancers (T) and autologous normal colon mucosa (NT) were quantified for the expression of 15 markers of the immune response with quantitiative reverse transcription-PCR (qRT-PCR). mRNA expression levels were correlated with MMR status. Immunohistochemistry (IHC) was performed using both interleukin 17 (IL17) and CD3 antibodies. RESULTS: Expression of cytotoxic markers (FasL, granzyme B and perforin), inflammatory cytokines (IL1beta, IL6, IL8, IL17 and transforming growth factor beta (TGFbeta)) and a marker of regulatory T cells (forkhead box P3 (Foxp3)) was significantly higher in tumours than in autologous normal tissues. Adjusting for MMR status, higher tumoural expression of both granzyme B and perforin was associated with the MSI-H phenotype, and the perforin T/NT ratio was higher in MSI-H tissues than in MSS tissues. Higher tumoural expression of Foxp3, IL17, IL1beta, IL6 and TGFbeta was associated with the MSS phenotype, and the IL17 T/NT ratio was higher in MSS tissues than in MSI-H tissues as assessed by both qRT-PCR and IHC. CONCLUSIONS: Immune gene expression profiling in CRC displayed different patterns according to MMR status. Higher Foxp3, IL6, TGFbeta and IL17 expression is a particular determinant in MMR-proficient CRC. These may be potential biomarkers for a new prognostic "test set" in sporadic CRCs.


Assuntos
Neoplasias Colorretais/imunologia , Reparo de Erro de Pareamento de DNA , Fatores de Transcrição Forkhead/metabolismo , Interleucina-17/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Complexo CD3/metabolismo , Colo/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Masculino , Estadiamento de Neoplasias , Fenótipo , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
10.
Gut ; 54(8): 1136-45, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15857934

RESUMO

BACKGROUND AND AIMS: Leptin, the product of the ob gene, has been suggested to increase the risk of colon cancer. However, we have shown that although leptin stimulates epithelial cell proliferation it reduces the development of carcinogen induced preneoplastic lesions in the rat colon. Here, we explored the effect of leptin in vitro on proliferation of human colon cancer cells, and in vivo on the growth of HT-29 xenografts in nude mice and the development of intestinal tumours in Apc(Min/+) mice. METHODS: Proliferation of HT-29, LoVo, Caco2, and SW 480 cells was assessed in the absence or presence of leptin (20-500 ng/ml) by 3H-thymidine incorporation and cell count. Leptin (800 microg/kg/day) or its vehicle was delivered for four weeks to nude mice, inoculated with HT-29 cells on day 0, and for six weeks to Apc(Min/+) mice. RESULTS: Leptin dose dependently stimulated cell DNA synthesis and growth in all cell lines. In nude mice, leptin caused a 4.3-fold increase in plasma leptin levels compared with pair fed controls. This hyperleptinaemia, despite leptin receptor expression in tumours, did not induce significant variation in tumour volume or weight. Tumour Ki-67 index was even inhibited. In leptin treated Apc(Min/+) mice, a 2.4-fold increase in plasma leptin levels did not modify the number, size, or distribution of intestinal adenomas compared with pair fed controls. CONCLUSIONS: Leptin acts as a growth factor on colon cancer cells in vitro but does not promote tumour growth in vivo in the two models tested. These findings do not support a pivotal role for hyperleptinaemia in intestinal carcinogenesis.


Assuntos
Neoplasias do Colo/patologia , Genes APC , Leptina/fisiologia , Adenoma/genética , Adenoma/patologia , Adenoma/fisiopatologia , Animais , Apoptose/fisiologia , Divisão Celular/fisiologia , Linhagem Celular Tumoral , Colo/patologia , Colo/fisiopatologia , Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , DNA de Neoplasias/biossíntese , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
11.
Gastroenterology ; 120(4): 857-66, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11231940

RESUMO

BACKGROUND & AIMS: The incidence of anal cancer is higher in patients with anal canal condyloma, a sexually transmitted disease, than in the general population. We determined the prevalence of anal dysplasia and cancer in patients with anal canal condyloma with respect to human immunodeficiency virus (HIV) status, immunity status, and human papillomavirus types. METHODS: In 174 consecutive patients (114 HIV positive, 60 HIV negative) with anal canal condyloma, lesions were cured, and the patients were then followed up prospectively. Langerhans cells (LCs) in normal anal mucosa were quantified, and viruses (Epstein-Barr virus, cytomegalovirus, human simplex virus 1, and various human papillomavirus [HPV] types) were characterized on inclusion. During follow-up (median 26 months), relapsed condylomas were resected and examined histologically. HIV load and CD4 T-lymphocyte counts in serum were determined at each visit. RESULTS: Several factors differed significantly between HIV-positive and HIV-negative patients: LCs/mm anal tissue (15 vs. 30), oncogenic HPV (27% vs. 13%), other current anal infections (44% vs. 0%), and sex ratio (93% vs. 73% male). During follow-up, condylomas relapsed in 75% of the HIV-positive patients, with 19 high-grade dysplasias (HGDs) and 1 invasive carcinoma, but in only 6% of HIV-negative patients, with 1 HGD. Male sex, HIV positivity, and <15 LCs/mm tissue were independent risk factors for condyloma relapse. HIV positivity, HGD before inclusion, and condyloma relapse were independent risk factors for HGD and cancer. Serum HIV load was associated with relapse, whereas CD4 T-lymphocyte counts were not. CONCLUSIONS: The prevalence of HGD and carcinoma is higher in HIV-positive than in HIV-negative patients, probably because of HPV activity. HIV-positive patients with high serum HIV load and/or a history of anal dysplasia should be examined by anoscopy, and condylomas should be analyzed histologically.


Assuntos
Doenças do Ânus/epidemiologia , Doenças do Ânus/virologia , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Adulto , Canal Anal/patologia , Doenças do Ânus/patologia , Condiloma Acuminado/virologia , Feminino , Seguimentos , França , Soronegatividade para HIV , Soropositividade para HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva
12.
Rev Prat ; 50(13): 1427-30, 2000 Sep 01.
Artigo em Francês | MEDLINE | ID: mdl-11019634

RESUMO

Helicobacter pylori is a risk factor for gastric carcinoma and an established carcinogenic bacterium. The relative risk to induce a gastric cancer is estimated to be 3 to 6 compared to that of individuals without H. pylori. Gastric atrophy and intestinal metaplasia in gastric mucosa are 2 well recognized precancerous lesions. Their occurrence and evolution are multifactorial depending on age at first infection, duration of infection and host's genetic characteristics. Prevention using H. pylori eradication is recommended only in individuals with high risk of cancer. Gastric lymphoma, although less frequent, may be due to H. pylori infection. Only in low grade lymphoma H. pylori eradication and periodic surveillance are recommended.


Assuntos
Adenocarcinoma/microbiologia , Infecções por Helicobacter , Helicobacter pylori , Linfoma/microbiologia , Neoplasias Gástricas/microbiologia , Adenocarcinoma/patologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Humanos , Linfoma/patologia , Fatores de Risco , Neoplasias Gástricas/patologia
13.
Gut ; 47(2): 178-83, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10896907

RESUMO

BACKGROUND AND AIM: The circulating peptide leptin produced by fat cells acts on central receptors to control food intake and body weight homeostasis. Contrary to initial reports, leptin expression has also been detected in the human placenta, muscles, and recently, in rat gastric chief cells. Here we investigate the possible presence of leptin and leptin receptor in the human stomach. METHODS: Leptin and leptin receptor expression were assessed by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and western blot analysis on biopsy samples from 24 normal individuals. Fourteen (10 healthy volunteers and four patients with non-ulcer dyspepsia and normal gastric mucosa histology) were analysed for gastric secretions. Plasma and fundic mucosa leptin content was determined by radioimmunoassay. RESULTS: In fundic biopsies from normal individuals, immunoreactive leptin cells were found in the lower half of the fundic glands. mRNA encoding ob protein was detected in the corpus of the human stomach. The amount of fundic leptin was 10.4 (3.7) ng leptin/g mucosa, as determined by radioimmunoassay. Intravenous infusions of pentagastrin or secretin caused an increase in circulating leptin levels and leptin release into the gastric juice. The leptin receptor was present in the basolateral membranes of fundic and antral gastric cells. mRNA encoding Ob-RL was detected in both the corpus and antrum, consistent with a protein of approximately 120 kDa detected by immunoblotting. CONCLUSION: These data provide the first evidence of the presence of leptin and leptin receptor proteins in the human stomach and suggest that gastric epithelial cells may be direct targets for leptin. Therefore, we conclude that leptin may have a physiological role in the human stomach, although much work is required to establish this.


Assuntos
Celulas Principais Gástricas/metabolismo , Leptina/biossíntese , Receptores de Superfície Celular , Receptores de Peptídeos/biossíntese , Adulto , Biópsia , Western Blotting , Proteínas de Transporte/metabolismo , Celulas Principais Gástricas/patologia , Feminino , Humanos , Imuno-Histoquímica , Leptina/análise , Masculino , Pessoa de Meia-Idade , Pentagastrina/farmacologia , RNA Mensageiro/análise , Radioimunoensaio , Receptores para Leptina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Secretina/fisiologia
14.
Dis Colon Rectum ; 41(11): 1454-7, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9823815

RESUMO

PURPOSE: The case of a human immunodeficiency virus-positive patient with rectal stenosis caused by a tumor that completely regressed in response to gancyclovir is presented. METHODS: Several biopsies from the tumoral mass failed to show any stigmata of non-Hodgkin's lymphoma, adenocarcinoma, or Kaposi sarcoma. No parasites could be detected in rectal biopsies. Viral inclusions showing both Epstein-Barr virus and cytomegalovirus on immunostained sections suggested an unusual form of viral infection. RESULTS: Antiviral therapy (gancyclovir 10 mg/kg/day) had a dramatic effect on pain and discharge of blood, and suppressed rectal difficulties within three days of therapy. The antiviral treatment was stopped at Day 10 because of leukopenia. Endoscopic and histologic examinations revealed normal rectal mucosa after 3, 6, 9, 12, and 18 months of follow-up. CONCLUSION: This is the first case of complete and long-term regression of a rectal stenosis secondary to a tumoral mass in response to antiviral therapy in patients with human immunodeficiency virus.


Assuntos
Antivirais/uso terapêutico , Ganciclovir/uso terapêutico , Infecções por HIV/complicações , HIV-1 , Neoplasias Retais/complicações , Reto/patologia , Constrição Patológica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/tratamento farmacológico , Resultado do Tratamento
15.
Presse Med ; 27(1): 20-1, 1998 Jan 10.
Artigo em Francês | MEDLINE | ID: mdl-9767760

RESUMO

The cause of chronic inflammatory bowel disease remains unknown. A genetic origin has been suggested by studies in twins. The gene or genes involved in Crohn's disease is probably situated on chromosome 16 and the genes involved in ulcerative colitis on chromosomes 2 and 7. It will undoubtedly take some time before the exact loci are precisely identified, but current research suggests that clinical applications are not far off.


Assuntos
Doença de Crohn/genética , Adolescente , Adulto , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 7 , Doença Crônica , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/genética , Doença de Crohn/epidemiologia , Doenças em Gêmeos/genética , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Judeus , Masculino , População Branca
16.
Gastroenterol Clin Biol ; 20(3): 243-7, 1996.
Artigo em Francês | MEDLINE | ID: mdl-8763061

RESUMO

OBJECTIVES: Diversion colitis is characterized by inflammatory lesions affecting colon or rectum excluded from the fecal stream for varied etiologies. These lesions may mimic both ulcerative colitis and Crohn's disease. The aim of our study was to examine the excluded rectum in patients with ulcerative colitis, and to study the evolution of the pathological lesions after ileo-rectal anastomosis. METHODS: Eighteen patients with ulcerative colitis treated by total colectomy before ileo-rectal anastomosis were studied. The pathological features i.e. glandular alteration, inflammatory infiltrate and mucosal ulceration or fissure, were studied during 3 periods: initial colectomy, excluded rectum at surgery for anastomosis and rectal biopsies after anastomosis. RESULTS: We observed on the excluded rectum a follicular lymphoid hyperplasia (18 cases), granulomas with giant cells (9 cases), mucosal fissures (9 cases). The inflammation extended to the submucosa in all cases and was occasionaly transmural. These lesions disappeared after the anastomosis and then seemed to be connected with the rectal diversion. CONCLUSIONS: The pathological changes of diversion proctitis that includes mucosal fissures, granulomas with giants cells or transmural inflammation, may lead to an erroneous diagnosis of Crohn's disease. The review of the previous colectomy is then mandatory to confirm the initial diagnosis of ulcerative colitis. These lesions disappear after anastomosis.


Assuntos
Hiperplasia do Linfonodo Gigante/etiologia , Colectomia/efeitos adversos , Colite Ulcerativa/cirurgia , Granuloma/etiologia , Doenças Retais/etiologia , Adolescente , Adulto , Anastomose Cirúrgica , Hiperplasia do Linfonodo Gigante/patologia , Feminino , Granuloma/patologia , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Doenças Retais/patologia , Reto/cirurgia , Reoperação , Estudos Retrospectivos , Fatores de Tempo
17.
Eur J Clin Invest ; 26(1): 53-8, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8682156

RESUMO

The authors have previously reported that platelet-activating factor (PAF), a phospholipid mediator with potent proinflammatory activities, is produced in the gastric mucosa and stimulates gastric acid secretion in humans and animals. In the present study they used the human gastric tumour cells HGT1 (clone 6) to examine whether PAF production is regulated by neuromediators. PAF was extracted by ethanol and assayed by the washed platelet aggregation test. HGT1 cells produced PAF spontaneously (110 +/- 20 pg 10(6) cells). The addition of vasoactive intestinal peptide (VIP; 10(-9) to 10(-7) mol L(-1)) or of histamine (10(-5) to 10(-3) mol L(-1)) increased PAF production by three- to fivefold, while the addition of carbachol (10(-7) to 10(-4) mol L(-1)) increased PAF production up to sevenfold. PAF production was also increased up to 10- to 13-fold, in a dose- and time-dependent manner, by the addition of calcium and two- to threefold by the addition of phorbol myristate acetate (PMA; 10(-7) to 10(-5) mol L(-1)). However, the addition of dibutyryl cyclic AMP (dBcAMP; 10(-6) to 10(-4) mol L(-1) was without any effect. This is the first report showing PAF production by gastric epithelial cells in response to histamine, VIP and carbachol. Furthermore, the findings are consistent with a central role of calcium in this production. The results of this study, together with those of previous studies from the authors' laboratory, support the hypothesis that PAF is a physiological mediator of gastric acid secretion.


Assuntos
Mucosa Gástrica/citologia , Fator de Ativação de Plaquetas/biossíntese , Animais , Calcimicina/farmacologia , Cálcio/farmacologia , Carbacol/farmacologia , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Histamina/farmacologia , Humanos , Ionóforos/farmacologia , Parassimpatomiméticos/farmacologia , Coelhos , Células Tumorais Cultivadas/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia
18.
Presse Med ; 24(2): 67-73, 75-6, 78-9, 1995 Jan 14.
Artigo em Francês | MEDLINE | ID: mdl-7899350

RESUMO

Helicobacter pylori is a microaerophilic bacterium initially found in the gastric antrum of patients with peptic ulcer disease. As a result, H. pylori is now believed to have a pathophysiologic role in gastritis as well as in peptic ulcer disease. Several recent studies showed that it may be associated with duodenal ulcer relapse and that eradication therapy using antibiotics may significantly decrease the ulcer recurrence rate in duodenal ulcer patients. Moreover, epidemiological studies suggest that it may increase the relative risk of carcinoma in the stomach and preliminary studies seem to indicate that some low-grade lymphoma in the stomach may regress after H. pylori eradication. Although the mechanisms by which H. pylori induces mucosal injury and/or neoplasm is not clearly understood, several modifications in gastric functions have been reported. The most specific way of detecting H. pylori in tissue is a combination of culture and histologic staining of mucosal biopsy specimens obtained by endoscopy. Rapid urease test, cytology and PCR procedures performed on biopsies may give rapid, sensitive and specific results. Breath test using 13C- or 14C-radiolabelled urea and serology tests are of particular importance when H. pylori diagnosis is needed via no invasive procedures. Helicobacter pylori is supposed to interact with G and D cells. Gastrin and somatostatin are synthetized and released from antral G and gastric D cells respectively. The gastric D cells are in close contact with either G and parietal cells. Gastrin stimulates gastric acid secretion and epithelial gastric cell proliferation (parietal and EC-L cells) while somatostatin inhibits these effects. Chronic gastritis is associated with fundic duodenal ulcer disease. In this situation, basal gastrin and meal- or bombesin-stimulated gastrin in the serum (especially gastrin G17) have been found to be higher in H. pylori positive than in negative patients. Moreover, gastrin decreases up to normal levels after eradication of H. pylori. The long term effect of a such hypergastrinemia is not so far established. The mechanism underlaying hormonal modification is poorly understood. Since no G/D cell ratio modification could be found after H. pylori eradication while the amount of somatostatin increases, one would suggest functional alteration of either G or D cells in the H. pylori-related chronic gastritis. The role of inflammatory mediators on the gastrin release and the processing of progastrin induced by the bacterium need further investigations.


Assuntos
Duodenopatias , Infecções por Helicobacter , Helicobacter pylori , Gastropatias , Gastropatias/microbiologia , Duodenopatias/tratamento farmacológico , Duodenopatias/microbiologia , Duodenopatias/fisiopatologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/patogenicidade , Humanos , Gastropatias/tratamento farmacológico , Gastropatias/fisiopatologia
19.
Gut ; 35(7): 905-8, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8063217

RESUMO

Ulcer recurrence is probably related to residual Helicobacter pylori (H pylori). Histological examination and culture are considered to be the most specific tests. CLO test is a rapid but less specific test, which is usually used as an alternative test to culture. The aim of this study was to investigate the efficiency of a simplified polymerase chain reaction (PCR) assay as a procedure for the diagnosis of gastric H pylori infection of patients. Biopsy specimens were obtained from antral mucosa of 58 patients at endoscopy and submitted to four tests for detection of H pylori. The bacteria were found in 53%, 43%, 48%, and 50% of patients according to the results of PCR, CLO test, culture, and histological examination. Twenty three patients had both negative histology and negative culture and PCR was negative in all of these. Thirteen patients were not classified because only histology or culture was positive and 10 of these had a positive PCR test. When the diagnosis of H pylori was established by agreement with both histology and culture or three positive tests out of four, 29 patients were H pylori positive (28 having had three positive tests and one displaying positive histology and culture), and 26 were negative, and three undetermined. PCR proved the most sensitive and specific test. These results suggest the simplified PCR assay may be a valuable test for the detection of H pylori.


Assuntos
Helicobacter pylori/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Úlcera Gástrica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Bacteriológicas , Sequência de Bases , Primers do DNA/genética , Feminino , Helicobacter pylori/genética , Técnicas Histológicas , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Sensibilidade e Especificidade
20.
Presse Med ; 23(19): 886-90, 1994 May 21.
Artigo em Francês | MEDLINE | ID: mdl-7937617

RESUMO

OBJECTIVES: Although the usual methods of exploring anorectal disorders give information on specific aspects of defecation, they do not take into account the related effect of disorders involving the pelvic contents including the genital and urinary tract. We therefore used physical examination and global imaging to demonstrate the effect of urinary and genital anomalies in female patients with dyschesia. METHODS: A prospective study was conducted in 50 consecutive female patients (age range 21-83) who consulted for dyschesia. The following protocol was used. History taking included a search for urinary and gynaecology surgery or medical treatment and the number of pregnancies and instrumental deliveries as well as a precise scoring of defecation disorders. The general physical examination included a search for signs of prolapsus or ulcerations. A rectocolpocystogram was performed in all patients. RESULTS: There were 7 patients under 40 years of age, 25 from 41 to 61 years and 18 over 61. Urinary incontinence was the most frequent functional complaint (80%). In 92% of the patients, the rectocolpocystogram revealed associated anatomic anomalies. Dynamic stimulation was associated with cervicocystoptosis (72%), hysteroptosis (50%) and rectocele (66%). CONCLUSION: Female dyschesia is a complex phenomena involving the anatomic status of the urinary, genital and anorectal tracts. Therapeutic management should be based on a complete examination including an evaluation of the pelvic contents and the perineum.


Assuntos
Constipação Intestinal/complicações , Prolapso Retal/complicações , Doenças da Bexiga Urinária/complicações , Incontinência Urinária por Estresse/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Constipação Intestinal/fisiopatologia , Cistoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Prolapso Retal/diagnóstico por imagem , Doenças da Bexiga Urinária/diagnóstico por imagem , Incontinência Urinária por Estresse/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA