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BACKGROUND & AIMS: The majority of patients with familial adenomatous polyposis (FAP) develop duodenal adenomas with a risk of progression to duodenal cancer. Endoscopic management of FAP duodenal adenomas has been proposed as a less-invasive option than surgery, but available data still are limited. Our aims were to assess the feasibility and safety of endoscopic treatment in duodenal polyposis and to evaluate its long-term efficacy in terms of recurrence and malignant degeneration. METHODS: FAP patients with stage IV duodenal polyposis were enrolled in 5 French centers as part of a national cohort and followed up for a median period of 5.66 years (interquartile range, 6.39 y). Primary outcomes were duodenal surgery-free and cancer-free survival. Two groups of patients were identified according to endoscopic procedures: group 1: resection and or destruction (by argon plasma coagulation) of duodenal polyps, and group 2: papillectomy. RESULTS: Fifty-eight patients were enrolled (29 men; median age, 44 y). Endoscopic therapy was performed in 37 patients in group 1 and in 19 patients in group 2. Duodenal cancer-free and surgery-free survival were 95.8% at 5 years and 92.6% at 10 years. Four patients required surgery and 2 patients developed cancers. In the 58 patients, the calculated Spigelman score decreased from 9.24 points at entry to 6.35 at 5 years and then plateaued. Complications (mostly bleeding and perforation) occurred in 20 patients. CONCLUSIONS: In this long-term cohort follow-up evaluation, endoscopic treatment of patients with severe duodenal polyposis appears relatively safe and effective as an alternative to surgery for the prevention of cancer.
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BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).
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Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Claritromicina/uso terapêutico , Claritromicina/administração & dosagem , Reação em Cadeia da Polimerase/métodos , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Idoso , Resultado do Tratamento , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Adulto JovemRESUMO
INTRODUCTION: Iron and vitamin B12 deficiencies are common in patients with atrophic gastritis, but there are limited data on the prevalence of these deficiencies in different types of atrophic gastritis. METHODS: This multicenter, prospective study assessed micronutrient concentrations in histologically confirmed autoimmune gastritis (AIG, n = 45), Helicobacter pylori-related non-autoimmune gastritis (NAIG, n = 109), and control patients (n = 201). A multivariate analysis was performed to determine factors influencing those deficiencies. RESULTS: The median vitamin B12 concentration was significantly lower in AIG (367.5 pg/mL, Q1, Q3: 235.5, 524.5) than in NAIG (445.0 pg/mL, Q1, Q3: 355.0, 565.0, p = 0.001) and control patients (391.0 pg/mL, Q1, Q3: 323.5, 488.7, p = 0.001). Vitamin B12 deficiency was found in 13.3%, 1.5%, and 2.8% of AIG, NAIG, and control patients, respectively. Similarly, the median ferritin concentration was significantly lower in AIG (39.5 ng/mL, Q1, Q3: 15.4, 98.3 ng/mL) than in NAIG (80.5 ng/mL, Q1, Q3: 43.6, 133.9, p = 0.04) and control patients (66.5 ng/mL, Q1, Q3: 33.4, 119.8, p = 0.007). Iron deficiency and iron deficiency adjusted to CRP were present in 28.9% and 33.3% of AIG, 12.8% and 16.5% of NAIG, and 12.9% and 18.4% of controls, respectively. Multivariate analysis demonstrated that AIG patients had a higher risk of developing vitamin B12 deficiency (OR: 11.52 [2.85-57.64, p = 0.001]) and iron deficiency (OR: 2.92 [1.32-6.30, p = 0.007]) compared to control patients. Factors like age, sex, and H. pylori status did not affect the occurrence of vitamin B12 or iron deficiency. CONCLUSION: Iron and vitamin B12 deficiencies are more commonly observed in patients with AIG than in those with NAIG or control patients. Therefore, it is essential to screen for both iron and vitamin B12 deficiencies in AIG patients and include the treatment of micronutrient deficiencies in the management of atrophic gastritis patients.
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Doenças Autoimunes , Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Deficiências de Ferro , Deficiência de Vitamina B 12 , Humanos , Gastrite Atrófica/complicações , Gastrite Atrófica/epidemiologia , Estudos Prospectivos , Ferro , Gastrite/complicações , Gastrite/epidemiologia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Vitamina B 12 , Micronutrientes , Doenças Autoimunes/complicaçõesRESUMO
BACKGROUND: Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15-25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. METHODS: We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. RESULTS: There were 70 patients (55/15 males, female respectively) with median age 60 (54-68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). CONCLUSIONS: Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.
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Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Neoplasias Colorretais/patologia , Feminino , Hepatectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. MATERIAL AND METHODS: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. RESULTS: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P = .015] and corpus AG [61.0% (95% CI 49.2; 72.0), P = .004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P = .068). CONCLUSION: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.
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Gastrite Atrófica/diagnóstico , Infecções por Helicobacter/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Biomarcadores/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , França/epidemiologia , Gastrinas/sangue , Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/epidemiologiaRESUMO
BACKGROUND AND AIMS: Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission. METHODS: In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade). Only patients without endoscopic recurrence (Rutgeerts i0 and i1) were then followed endoscopically and clinically (median follow-up 38 months). RESULTS: At the time of the first postoperative colonoscopy, 18 patients (72%) were in endoscopic remission, and 7 (28%) experienced an endoscopic recurrence (Rutgeerts ≥i2). The Rutgeerts score was significantly correlated with the Watson score (ρ = 0 .73; P < .0001). The Watson scores at baseline were significantly higher in patients with further endoscopic recurrence (median 2.0; interquartile range [IQR] 1.5-2.0) than in those with endoscopic remission (median 1.0; IQR 1.0-1.0; P = .032) and were significantly higher in patients with clinical relapse (medium 2.0, IQR 2.0-2.0) compared with those in clinical remission (median 1.0; IQR 1.0-1.0; P = .036). CONCLUSIONS: CLE could be useful in monitoring patients with CD after intestinal resection. Further studies with a larger population are necessary to confirm these preliminary results.
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Colo/cirurgia , Doença de Crohn/cirurgia , Íleo/cirurgia , Adulto , Colectomia , Colo/patologia , Colonoscopia , Doença de Crohn/patologia , Feminino , Humanos , Íleo/patologia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Recidiva , Medição de Risco , Adulto JovemRESUMO
BACKGROUND: Colonoscopy with pan-chromoendoscopy (CE) is superior to standard colonoscopy in detecting neoplasia in patients with IBD. Performing random biopsies in unsuspicious mucosa after CE remains controversial. METHODS: Consecutive patients with IBD who underwent surveillance colonoscopy using CE were prospectively included. The standardised procedure used CE, performed targeted biopsies or endoscopic resection on suspicious lesions and then quadrant random biopsies every 10â cm. A panel of five expert pathologists reviewed histological slides with dysplasia. Logistic regression model was used to evidence the factors associated with neoplasia in any or in random biopsies. RESULTS: 1000 colonoscopes were performed in 1000 patients (495 UC, 505 Crohn's colitis). In 82 patients, neoplasia was detected from targeted biopsies or removed lesions, and among them dysplasia was detected also by random biopsies in 7 patients. Importantly, in 12 additional patients dysplasia was only detected by random biopsies. Overall, 140 neoplastic sites were found in 94 patients, 112 (80%) from targeted biopsies or removed lesions and 28 (20%) by random biopsies. The yield of neoplasia by random biopsies only was 0.2% per-biopsy (68/31â 865), 1.2% per-colonoscopy (12/1000) but 12.8% per-patient with neoplasia (12/94). Dysplasia detected by random biopsies was associated with a personal history of neoplasia, a tubular appearing colon and the presence of primary sclerosing cholangitis (PSC). CONCLUSIONS: Despite their low yield, random biopsies should be performed in association with CE in patients with IBD with a personal history of neoplasia, concomitant PSC or a tubular colon during colonoscopy. TRIAL REGISTRATION NUMBER: IRB 001508, Paris 7 University.
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Biópsia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Gastroenterologia , Aumento da Imagem/métodos , Doenças Inflamatórias Intestinais/complicações , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia/métodos , Colite Ulcerativa/complicações , Neoplasias Colorretais/cirurgia , Doença de Crohn/complicações , Feminino , Seguimentos , França , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Imagem de Banda Estreita , Vigilância da População/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours. In particular, metabolic alteration in cancer cells are coupled to the modulation of intracellular and extracellular pH, epithelial-to-mesenchymal transition and associated increased invasiveness, autophagy, and the development of anticancer treatment resistance. Finally, based on mechanistic, pre-clinical and clinical studies, we proposed the adjuvant supplementation of dietary n-3 polyunsaturated fatty acids for a complementary holistic treatment of the cancer disease.
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Antineoplásicos/uso terapêutico , Gorduras na Dieta/administração & dosagem , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Progressão da Doença , Transição Epitelial-Mesenquimal , Humanos , Mitocôndrias/metabolismo , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
BACKGROUND AND AIMS: One of the reasons for the failure of infliximab (IFX) is immediate hypersensitivity reactions (IHR). We aimed to report the efficacy and safety of a tolerance induction protocol in inflammatory bowel diseases (IBD) patients who had previously experienced IHR during IFX infusions. PATIENTS AND METHODS: We reported all cases of IBD patients who had previously experienced IHR due to IFX and who were submitted to a standardized protocol of tolerance induction to IFX from 2010 to 2015. RESULTS: IHR occurred in a majority of patients (69%) during the first 3 infusions and for half of them after a period of IFX withdrawn. Skin prick tests were negative and only 2 intradermal tests were positive. Basophil activation tests and antidrug antibody measurements were performed in 8 out of 16 patients and were positive in 3 and 4 patients respectively. Induction of tolerance was successful in 69% of patients and IFX was pursued with clinical efficacy > 1 year in 7 patients (44%). Allergologic investigations were not predictive of tolerance induction success. CONCLUSION: A majority of IHR to IFX infusions occurred during the beginning or restarting of treatment and was related to a nonallergic hypersensitivity. Induction of tolerance to IFX is feasible and effective and may safely allow retreatment of IFX in almost 70% of IBD patients.
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Hipersensibilidade a Drogas/etiologia , Tolerância a Medicamentos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Adulto , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Hipersensibilidade Imediata/induzido quimicamente , Infliximab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Inflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow-up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues. An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B1 magnetic field, and a dedicated ERC was used for signal reception. Colon-wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 µL to 2 µL while keeping acquisition times below 3 min. The acquired spectra show various biochemical contents such as α- and ß-methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon-wall complex exhibits both high lipid and high water contents. To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies.
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Colo/diagnóstico por imagem , Imageamento por Ressonância Magnética/instrumentação , Espectroscopia de Ressonância Magnética/instrumentação , Animais , Colite/diagnóstico por imagem , CamundongosRESUMO
Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4â% in the BWIC group versus 37.5â% in the standard colonoscopy group (odds ratio [OR] 1.13; 95â% confidence interval [CI] 0.87â-â1.48; Pâ=â0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; Pâ=â0.005). For advanced adenomas, the results were 50 (10.2â%) and 36 (7.3â%), respectively (Pâ=â0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; Pâ<â0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. CLINICAL TRIALS REGISTRATION: EudraCT 2012-A00548â-â35; NCT01937429.
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Adenocarcinoma/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagem , Idoso , Ceco , Cor , Feminino , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , ÁguaRESUMO
A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.
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Dispepsia/epidemiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Úlcera Péptica/epidemiologia , Anemia Perniciosa/epidemiologia , Anemia Perniciosa/etiologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Cirurgia Bariátrica/efeitos adversos , Dispepsia/patologia , Esofagite Eosinofílica/epidemiologia , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Humanos , Úlcera Péptica/patologiaRESUMO
BACKGROUND: Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn's disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients. AIM AND METHODS: We report three cases of patients with isolated Crohn's ileitis associated with PSC and in whom colonic inflammation was never documented. RESULTS: Patients were followed up 10-23 years and each patient underwent 6-7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9-10 years. CONCLUSIONS: Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept that colonic mucosal inflammation is critical for the pathogenesis of PSC in inflammatory bowel disease.
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Colangite Esclerosante/complicações , Doença de Crohn/complicações , Ileíte/complicações , Adulto , Idoso , Colangite Esclerosante/diagnóstico , Doença de Crohn/diagnóstico , Feminino , Humanos , Ileíte/diagnóstico , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: An endoluminal magnetic resonance (MR) imaging protocol including the design of an endoluminal coil (EC) was defined for high-spatial-resolution MR imaging of mice gastrointestinal walls at 4.7 T. MATERIALS AND METHODS: A receive-only radiofrequency single-loop coil was developed for mice colon wall imaging. Combined with a specific protocol, the prototype was first characterized in vitro on phantoms and on vegetables. Signal-to-noise ratio (SNR) profiles were compared with a quadrature volume birdcage coil (QVBC). Endoluminal MR imaging protocol combined with the EC was assessed in vivo on mice. RESULTS: The SNR measured close to the coil is significantly higher (10 times and up to 3 mm of the EC center) than the SNR measured with the QVBC. The gain in SNR can be used to reduce the in-plane pixel size up to 39 × 39 µm(2) (234 µm slice thickness) without time penalty. The different colon wall layers can only be distinguished on images acquired with the EC. CONCLUSION: Dedicated EC provides suitable images for the assessment of mice colon wall layers. This proof of concept provides gains in spatial resolution and leads to adequate protocols for the assessment of human colorectal cancer, and can now be used as a new imaging tool for a better understanding of the pathology.
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Colite/diagnóstico por imagem , Colo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Animais , Modelos Animais de Doenças , Processamento de Imagem Assistida por Computador , Camundongos , Cebolas , Imagens de Fantasmas , Reto/diagnóstico por imagem , Razão Sinal-RuídoRESUMO
OBJECTIVES: Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated with the severity of endoscopic lesions in Crohn's disease (CD). We analyzed the relationships between levels of fCal and high-sensitivity C-reactive protein (hsCRP) and the presence and severity of postoperative endoscopic recurrence in asymptomatic CD patients (Harvey-Bradshaw index≤3). METHODS: Blood and fecal samples were collected in consecutive asymptomatic CD patients (Harvey-Bradshaw index 0.85 ± 0.19, mean ± s.e.m.) who had undergone an ileocolonic resection. hsCRP and fCal were measured and a routine ileocolonoscopy was performed within 18 months (median 7 months) from resection, to detect endoscopic recurrence according to the Rutgeerts score. RESULTS: Eighty-six patients were included in this prospective multicenter observational cohort. fCal concentrations differed significantly in patients with endoscopic recurrence when compared with those in endoscopic remission (mean ± s.e.m.: 473 ± 78 µg/g vs. 115 ± 18 µg/g; P<0.0001). The area under the receiver operating characteristic (ROC) curve to discriminate between patients in endoscopic remission and recurrence was 0.86 for fCal and lower for hsCRP (0.70). The best cutoff point for fCal to distinguish between endoscopic remission and recurrence was 100 µg/g as determined by the ROC curve, and its sensitivity, specificity, positive and negative predictive values (NPVs), as well as overall accuracy were 95%, 54%, 69%, 93%, and 77%, respectively. CONCLUSION: Measurement of fCal concentrations is a promising and useful tool for monitoring asymptomatic CD patients after ileocolonic resection. Taking into account the high NPV of fCal, a threshold below 100 µg/g could avoid systematic ileocolonoscopies in 30% of patients from this population.
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Proteína C-Reativa/metabolismo , Colectomia , Doença de Crohn/cirurgia , Fezes/química , Íleo/cirurgia , Complexo Antígeno L1 Leucocitário/metabolismo , Adolescente , Adulto , Idoso , Doenças Assintomáticas , Estudos de Coortes , Doença de Crohn/metabolismo , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: In Lynch syndrome, flat and diminutive adenomas are particularly prone to malignant transformation, but they can be missed by standard colonoscopy. It is not known whether chromocolonoscopy is able to detect more adenomas than standard colonoscopy in patients with Lynch syndrome. METHODS: We conducted a prospective, multicenter, randomized trial to compare standard colonoscopy with standard colonoscopy followed by pancolonic chromoscopy with indigo carmine in patients with a proven germline mutation in a mismatch-repair gene related to Lynch syndrome and who were undergoing screening or surveillance colonoscopy. Standard colonoscopy was used first to detect visible lesions. Colonoscopy with chromoscopy was then performed by a second gastroenterologist (blinded to the findings of the first colonoscopy) to detect additional lesions. The primary end point was the number of patients in whom at least one adenoma was detected. RESULTS: A total of 78 eligible patients (median age, 45 years) were enrolled at 10 centers from July 2008 to August 2009. Significantly more patients with at least one adenoma were identified by chromocolonoscopy (32/78 (41%)) than by standard colonoscopy (18/78 (23%); P<0.001). The percentage of patients in whom at least one additional adenoma was detected during the chromoscopy was 31% (24/78). Overall, chromocolonoscopy plus colonoscopy detected a total of 55 adenomas in 32 patients (mean number of adenomas detected per patient: 0.7 vs. standard colonoscopy alone: 0.3; P<0.001). CONCLUSION: The results support the proposition that chromocolonoscopy may significantly improve the detection rate of colorectal adenomas in patients undergoing screening or surveillance colonoscopy for Lynch syndrome.
Assuntos
Adenoma/patologia , Carcinoma/patologia , Colonoscopia/métodos , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Neoplasias Colorretais/patologia , Corantes , Detecção Precoce de Câncer/métodos , Índigo Carmim , Adenoma/diagnóstico , Adenoma/etiologia , Adulto , Carcinoma/diagnóstico , Carcinoma/etiologia , Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etiologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reto/patologia , Método Simples-CegoRESUMO
BACKGROUND: Patients with familial adenomatous polyposis (FAP) and severe (stage IV) duodenal polyposis are candidates for pancreaticoduodenectomy, which has high morbidity. Little information is available about the feasibility of therapeutic endoscopy for these patients. OBJECTIVE: To evaluate the long-term efficiency and risks of endoscopic therapy. DESIGN: Retrospective study. SETTING: A 2-referral center long-term cohort study. PATIENTS: Thirty-five FAP patients (15 men, mean age 48 years) presenting with stage IV duodenal polyposis were included. Patients had a mean Spigelman classification score of 9.8 points (range 9-12 points) at their first examination. INTERVENTIONS: Patients underwent a surveillance endoscopy, including lateral and axial viewing with chromoendoscopy while under sedation, along with 7 ± 4.8 therapeutic endoscopic sessions during a follow-up period of 9 ± 4.5 years (range 1-19 years) after their first endoscopy. MAIN OUTCOME MEASUREMENTS: Treatment modalities, adverse events, and efficiency (evolution of the Spigelman score) were reviewed. RESULTS: A total of 245 therapeutic endoscopies were performed and 15 adverse events (6%) occurred. During the follow-up period, Spigelman scores decreased in 95% of patients by 6 ± 2.2 points (P = .002). Modeling analysis showed that the mean Spigelman score decreased by 60% after 150 months. LIMITATIONS: Retrospective study and the duration of the follow-up, even though this is the longest follow-up reported in medical literature. CONCLUSION: Endoscopic treatment of severe duodenal polyposis in patients with FAP produces few adverse events and allows efficient downstaging of the polyposis. Long-term follow-up data did not reveal a high risk of invasive duodenal cancer in these patients.
Assuntos
Polipose Adenomatosa do Colo/cirurgia , Neoplasias Duodenais/cirurgia , Duodeno/cirurgia , Endoscopia do Sistema Digestório/métodos , Mucosa Intestinal/cirurgia , Adulto , Coagulação com Plasma de Argônio/métodos , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. Results: The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.
RESUMO
A differential responsiveness of patients to ionizing radiation is observed after preoperative radiotherapy for rectal adenocarcinoma that might be related, in part, to an apoptosis defect. To establish if proteins of the apoptotic cascades [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480) and radiosensitive (SW48) human colorectal cell lines. We demonstrated that, after irradiation, the SW48 cells increased the expression of the pro-apoptotic proteins, whereas the SW480 cells increased the expression of the anti-apoptotic protein XIAP. Moreover, XIAP knockdown in SW480 cells enhanced the basal and radiation-induced apoptotic index; the propensity of the SW480 cells to undergo apoptosis after radiation was higher compared with SW48 cells. In a translational study of 38 patients with rectal carcinoma, we analyzed the apoptotic profile for tumor and noncancerous tissue for each biopsy specimen using IHC. According to their response to preoperative radiotherapy, patients were classified into two groups: responsive and nonresponsive. Although no difference in expression of caspase 3, 8, or 9 was observed in the tumor/normal tissue ratio between responsive and nonresponsive patients, the ratio decreased for DIABLO and increased for XIAP. In conclusion, inhibition of XIAP rescues cellular radiosensitivity and both DIABLO and XIAP might be potential predictive markers of radiation responsiveness in rectal adenocarcinoma.
Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/radioterapia , Biomarcadores Tumorais/metabolismo , Tolerância a Radiação , Neoplasias Retais/metabolismo , Neoplasias Retais/radioterapia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose , Proteínas de Transporte/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Proteínas Mitocondriais/metabolismo , Prognóstico , Tolerância a Radiação/efeitos da radiação , Radiação Ionizante , Neoplasias Retais/enzimologia , Neoplasias Retais/patologiaRESUMO
BACKGROUND: Serum pepsinogen (PG) testing is recommended by the European guidelines for diagnosis of chronic atrophic gastritis (CAG). However, wide variations in diagnostic performances are observed, due to the differences in the extent of gastric atrophy, and possibly in its origin (Helicobacter pylori-, autoimmune (AIG)). AIM: To analyze the diagnostic performances of PGs testing according to these different parameters, using enzyme-linked-immunosorbent serologic assay (ELISA) and chemiluminescent immunoassay (CLEIA). METHODS: Serum samples from patients having undergone gastroscopy with biopsies in five French centers were collected prospectively. Sensitivity (Se), specificity (Sp), and Area Under Curve were analyzed according to the extent and origin of CAG. RESULTS: Overall, 344 patients (156 males [45%]; mean age 58.8 [±14.2] years) were included, among whom 44 had AIG. Diagnostic performances of PG I for the detection of corpus CAG were excellent, with Se and Sp of 92.7% and 99.1% for ELISA and 90.5% and 98.2% for CLEIA, respectively. For AIG, corresponding values were 97.7% and 97.4% for ELISA, and 95.6% and 97.1% for CLEIA. In multivariate analysis, PG levels were associated with the auto-immune origin (p<0.001) but not with the extent of the atrophic gastritis. CONCLUSIONS: Pepsinogens are highly efficient for the diagnosis of corpus-limited CAG and allow to discriminate AIG from H. pylori-induced gastritis.