RESUMO
In the management of ulcerative colitis (UC), colonoscopy (CS) is considered essential for diagnosis;however, its invasiveness poses a challenge. Conversely, recent advancements in ultrasound diagnostic devices have improved imaging quality for the digestive tract, rendering them valuable in UC management. Therefore, this study aimed to elucidate the correlation between abdominal ultrasonography (AUS) and CS in assessing UC activity. The indices adopted for UC evaluation using AUS were as follows:1) bowel wall stratification, 2) bowel wall thickness, 3) bowel wall flow at power Doppler, 4) presence of increased brightness of inflammatory fat, and 5) presence of mesenteric lymph node swelling greater than 5mm. Subsequently, we developed a new AUS index for UC, termed the UCUS score, which comprises the aforementioned five indices. Finally, we compared the UCUS score with representative endoscopic indices, the Mayo endoscopic sub-score, and the Ulcerative Colitis Endoscopic Index of Severity. The results demonstrated that our proposed UCUS score better reflected disease activity than individual items assessed separately. ROC curve analysis revealed a UCUS score cutoff of 3 points. Therefore, a UCUS score of ≥3 points indicates the need for further examination with CS. Conversely, a score below 3 points suggests low disease activity, and in situations when evaluating treatment effectiveness, AUS could potentially substitute for CS. We believe that the UCUS score is an important source of information to understand the patient's condition and to motivate the patient to undergo endoscopy.
Assuntos
Colite Ulcerativa , Ultrassonografia , Colite Ulcerativa/diagnóstico por imagem , Humanos , Abdome/diagnóstico por imagem , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Although evidence for the short- to medium-term efficacy of adalimumab in ulcerative colitis (UC) patients is emerging, there are a limited number of reports on the long-term efficacy of adalimumab. This study was to understand baseline demographic features, which potentially could be risk factors for relapse or colectomy following induction of remission by adalimumab in UC patients. Additionally, factors affecting long-term outcomes were to be identified. METHODS: Twenty-one patients with UC who had been treated with adalimumab were reviewed retrospectively. Comparative analyses were undertaken by factoring steroid withdrawal versus non-withdrawal, long-term remission versus relapse following remission, and requiring surgical intervention for UC versus surgery-free. RESULTS: Adalimumab treatment was associated with steroid tapering in steroid-dependent cases in the long term. Of the 14 patients in whom clinical remission was achieved, the cumulative nonrelapse survival rate at 350 weeks was 43.8% and the cumulative nonoperative survival rate was 85.7%. Risk factors for surgery included intolerance to salicylates (p = 0.005) and past treatment with tacrolimus (p = 0.023). CONCLUSIONS: Adalimumab treatment was associated with long-term efficacy in patients with mild UC - patients achieved a high cumulative nonoperative survival rate over a long period of time, beyond 6 years.
Assuntos
Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Padrões de Prática Médica , Adolescente , Adulto , Idoso , Proteína C-Reativa/metabolismo , Colectomia , Colite Ulcerativa/cirurgia , Feminino , Humanos , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND & AIMS: A random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC. METHODS: We performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups. RESULTS: The mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679-2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation. CONCLUSIONS: In a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608.
Assuntos
Biópsia/métodos , Colite Ulcerativa/complicações , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Vigilância da População , Adulto , Colonoscopia , Neoplasias Colorretais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da CirurgiaRESUMO
OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.
Assuntos
Adenoma/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonografia Tomográfica Computadorizada , Neoplasias Colorretais/diagnóstico por imagem , Gastroenterologistas , Radiologistas , Adenoma/patologia , Idoso , Carcinoma/patologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/patologia , Fezes/química , Feminino , Hemoglobinas/análise , Humanos , Imunoquímica , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Efficacy of maintenance therapy in ulcerative colitis (UC) in the remission stage has been reported to depend on release profile or dosing regimen of oral 5-aminosalicylic acid (5-ASA) products used. Aim of this study is to investigate real life results in using oral 5-ASA products for maintaining mild to moderate UC patients in Japan. METHODS: Adult UC outpatients treated with oral 5-ASA products were enrolled from 379 sites in Japan between July 2012 and July 2013, and followed for 52 weeks. Remission maintenance rate was evaluated by products and dosages. Factors affecting recurrence were also examined. RESULTS: A total of 5695 UC patients were registered. Among the 4677 patients in whom remission maintenance was observed, remission maintenance rate at week 52 was 80.2%. As for disease duration and dosage, Pentasa® 4000 mg/day in 2 divided doses was administered to 480 (21.0%) patients in remission and 341 (46.6%) patients in active stage, and Asacol® 3600 mg/day in 3 divided doses was administered to 696 (46.4%) patients in remission and 473 (67.3%) patients in active stage. The remission maintenance rate at week 52 by dosage and frequency did not significantly differ between Pentasa® Tablets at 4000 mg/day in 2 divided doses (76.5%) and Asacol® Tablets at 3600 mg/day in 3 divided doses (76.1%, P = 0.7868). Factors affecting the risk of relapse in UC were identified. Significantly persistent remission maintenance was noted in patients in whom duration of remission maintenance until enrollment was 12 to <24 months or ≥24 months relative to the reference category of <3 months (12 to <24 months: HR 0.600 [0.486-0.740], p < 0.0001]; ≥24 months: HR 0.352 [0.289-0.431], p < 0.0001). CONCLUSIONS: Efficacy of real life results in using oral 5-ASA products for maintaining mild to moderate UC patients was favorable. Maintaining remission for 12 months or longer after induction therapy was shown to reduce recurrence risk thereafter. TRIAL REGISTRATION: UMIN 000008563 (the date of registration: July 30, 2012), ClinicalTrials.gov NCT01654783 (the date of registration: July 30, 2012).
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Sulfassalazina/uso terapêutico , Administração Oral , Adulto , Idoso , Composição de Medicamentos , Feminino , Humanos , Japão , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Recidiva , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND/AIMS: In patients with active ulcerative colitis (UC), pharmacologics, although initially effective in most patients, are associated with refractoriness, loss of response or unfavourable side effects as additional morbidity factors. Depletion of myeloid lineage leucocytes like the CD14(+)CD16(+) monocyte phenotype, which is a major source of tumour necrosis factor-α, by granulocyte/monocyte apheresis (GMA) if effective, is also known to be free from side effects. METHODS: In clinical practice setting, 77 consecutive patients with moderate to severe UC, who failed to respond to first-line medications received GMA with the Adacolumn as remission induction therapy. Patients who achieved remission were followed for 3 years. RESULTS: Among the 77 patients, 46.8% were corticosteroids-naïve, 26% corticosteroid-dependent and 27.3% corticosteroid-refractory. The overall clinical remission rate was 79.2%, and the overall mucosal healing (MH) rate according to the Mayo endoscopic subscore ≤1 was 58.5%. MH rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 70.8, 56.3, and 38.5%, respectively. The 3-year sustained clinical remission rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 83.3, 68.8, and 23.1%, respectively. CONCLUSION: Corticosteroid-naïve patients appeared to benefit the most from the Adacolumn GMA, and attain a favourable long-term clinical course. Accordingly, GMA should be a first-line therapy in this clinical setting.
Assuntos
Colite Ulcerativa/terapia , Glucocorticoides/uso terapêutico , Leucaférese , Monócitos/imunologia , Adsorção , Adulto , Colite Ulcerativa/imunologia , Resistência a Medicamentos , Feminino , Glucocorticoides/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: The value of enteral nutrition (EN) as maintenance therapy in patients with quiescent Crohn's disease (CD) has not been fully evaluated. The purpose of this study was to review the efficacy of EN for the maintenance of remission in patients with quiescent CD. METHODS: Seven prospective cohort studies evaluating the efficacy of EN for the maintenance of remission in quiescent CD were included. Three of the seven studies were randomized-controlled trials (RCTs). In all studies, patients used EN as a supplement or as a nocturnal tube feeding in addition to their normal food. RESULTS: One study compared the efficacy of elemental diet and polymeric diet. Elemental and polymeric diets were equally effective for the maintenance of clinical remission and for allowing tapering and cessation of steroid therapy. The other six studies compared the outcomes between patients treated with and without EN. The maintained clinical remission rate at 1 year was significantly higher in patients treated with EN in four of the six studies. Quantitative pooling of the studies was not feasible due to a small number of RCTs and a narrative account of the study characteristics. CONCLUSIONS: Our review suggests that EN is useful for the maintenance of remission in patients with quiescent CD. However, there are several limitations in the reviewed studies. There are few RCTs. Further, the sample size is small, and the duration of intervention and follow-up is short. Large and well-designed RCTs should be conducted to rigorously evaluate the efficacy of EN for maintaining remission.
Assuntos
Doença de Crohn/terapia , Nutrição Enteral/tendências , Indução de Remissão , Humanos , Inflamação/patologia , Mucosa Intestinal/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Osteopenia and osteoporosis are considered to be extra-intestinal manifestations of inflammatory bowel disease (IBD). Anti-tumor necrosis factor (TNF)-α biologics have been introduced as novel medications for an active IBD. However, it is still not well documented whether anti-TNF-α affects the frequency of bone loss or abnormality of bone mineral markers among patients with IBD. AIMS: This study was to investigate the biochemical basis of low bone mineral density (BMD) and increased turnover in IBD during infliximab (IFX) therapy. METHODS: Forty patients with Crohn's disease (CD), 80 patients with ulcerative colitis (UC), and 65 age- and gender-matched controls were included. BMD was measured with dual-energy X-ray absorptiometry, and vitamins K and D were measured as serum undercarboxylated osteocalcin (ucOC) and 1,25-(OH)2D, respectively. Bone formation and resorption were based on measuring bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx), respectively. RESULTS: Significantly lower BMD was found in patients with UC and CD as compared to controls (P < 0.05). BAP, 1,25-(OH)2D, ucOC, and NTx were significantly higher in CD patients, but not in UC patients as compared to controls (P < 0.05). Further, serum NTx level was significantly higher in CD patients who were receiving IFX as compared to CD patients who were not receiving IFX (P < 0.01). CONCLUSIONS: A lower BMD and higher bone metabolism markers were found in CD patients as compared to controls or UC patients. A significant increased serum level of NTx, a biochemical marker of increased bone resorption, was observed in CD patients during IFX therapy.
Assuntos
Anti-Inflamatórios/uso terapêutico , Reabsorção Óssea/sangue , Osso e Ossos/efeitos dos fármacos , Colite Ulcerativa/tratamento farmacológico , Colágeno Tipo I/sangue , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Peptídeos/sangue , Absorciometria de Fóton , Adulto , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese/efeitos dos fármacos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. METHODS: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). RESULTS: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/µL to 6950/µL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. CONCLUSIONS: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.
Assuntos
Doença de Crohn/terapia , Granulócitos , Leucaférese/métodos , Monócitos , Adolescente , Adsorção , Adulto , Idoso , Criança , Doença de Crohn/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
We describe a rare case of ulcerative colitis (UC) with lymphoid follicular proctitis (LFP) extending discontinuously from the rectum to the ascending colon. The patient was a 42-year-old female presenting with a positive fecal occult blood test. Colonoscopy revealed erosions and disappearance of vascular patterns in the ascending colon and lower rectum, together with circumferential, uniform, granular lesions in the lower rectum. Histological examinations of the rectal biopsy specimens revealed lymphoid follicles, hyperplasia, and infiltration of chronic inflammatory cells. We suspected rectal and segmental UC with LFP. Initially, the patient was managed conservatively because of the lack of symptoms; however, on developing mucoid stools and haematochezia, mesalazine administration was started. Her symptoms and endoscopic findings resolved completely. LFP is closely associated with UC. Therefore, while diagnosing and managing LFP, it is necessary to ascertain or rule out potential complications.
Assuntos
Colite Ulcerativa/complicações , Proctite/complicações , Adulto , Feminino , Humanos , Proctite/patologiaRESUMO
A tractor-based robot with the capability of real-time assessing and visualizing the radioactive material density and fertility distribution of farmlands has been developed to accelerate the recovery process of the farmlands suffered by the accident of the Fukushima Daiichi Nuclear Power Plant (FDNPP). In a field test at a decontaminated farmland near FDNPP, within-field heterogeneities of soil contamination and fertility are clarified almost in real-time. Results obtained by this robot are consistent with the map by the conventional soil sampling or the history of decontamination activities.
Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação , Robótica , Poluentes Radioativos do Solo , Radioisótopos de Césio/análise , Fazendas , Fertilidade , Japão , Centrais Nucleares , Monitoramento de Radiação/métodos , Solo , Poluentes Radioativos do Solo/análiseRESUMO
BACKGROUND AND AIMS: Mosaic chromosomal alterations [mCAs] increase the risk for haematopoietic malignancies and may be risk factors for several other diseases. Inflammatory bowel diseases [IBDs], including Crohn's disease [CD] and ulcerative colitis [UC], are associated with mCAs, and patients may be at risk for haematopoietic malignancy development and/or modification of IBD phenotypes. In the present study, we screened patients with IBD for the presence of mCAs and explored the possible pathophysiological and genetic risk factors for mCAs. METHODS: We analysed mCAs in peripheral blood from 3339 patients with IBD and investigated the clinical and genetic risk factors for mCAs. RESULTS: CD and exposure to thiopurines before the age of 20 years were identified as novel independent risk factors for mCAs [odds ratio = 2.15 and 5.68, p = 1.17e-2 and 1.60e-3, respectively]. In contrast, there were no significant associations of disease duration, anti-tumour necrosis factor alpha antibodies, or other clinical factors with mCAs. Gene ontology enrichment analysis revealed that genes specifically located in the mCAs in patients with CD were significantly associated with factors related to mucosal immune responses. A genome-wide association study revealed that ERBIN, CD96, and AC068672.2 were significantly associated with mCAs in patients with CD [p = 1.56e-8, 1.65e-8, and 4.92e-8, respectively]. CONCLUSIONS: The difference in mCAs between patients with CD and UC supports the higher incidence of haematopoietic malignancies in CD. Caution should be exercised when using thiopurines in young patients with IBD, particularly CD, in light of possible chromosomal alterations.
Assuntos
Colite Ulcerativa , Doença de Crohn , Neoplasias Hematológicas , Doenças Inflamatórias Intestinais , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Estudo de Associação Genômica Ampla , Humanos , Fatores Imunológicos , Doenças Inflamatórias Intestinais/complicações , Fatores de RiscoRESUMO
BACKGROUND: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. METHODS: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. RESULTS: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). CONCLUSIONS: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.
Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Proteínas RGS , Anti-Inflamatórios não Esteroides/efeitos adversos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Patrimônio Genético , Estudo de Associação Genômica Ampla , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Japão/epidemiologia , Mesalamina/efeitos adversos , Modelos Estatísticos , PrognósticoRESUMO
We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger's clinical activity index (CAI) from 11.7±2.6 at baseline to 6.6±4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI≤4 or ΔCAI≥3), and 7 (35%) achieved complete remission (CAI≤4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.
Assuntos
Colite Ulcerativa/terapia , Leucaférese/métodos , Esteroides/uso terapêutico , Adolescente , Adulto , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Segurança , Resultado do TratamentoRESUMO
Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn's disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4â14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2 µg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1 µg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4-14 days after ADA administration was ≥9.2 µg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1 µg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.
Assuntos
Adalimumab/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adalimumab/sangue , Adalimumab/uso terapêutico , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/sangue , Curva ROC , Estudos RetrospectivosRESUMO
Pneumatosis cystoides intestinalis (PCI) is associated with various diseases, but rarely with inflammatory bowel disease. We describe a rare case of PCI associated with ulcerative colitis. The patient was a 30-year-old man with ulcerative colitis (UC), which was in remission under immunomodulator therapy. Colonoscopic examination around 2 years after a diagnosis of UC revealed multiple hemispherical submucosal tumors (SMT) in the ascending colon and hepatic flexure, with erosion and disappearance of vascular network patterns in the rectum. PCI was diagnosed from the result of colonoscopic examination and computed tomography, and had not changed on colonoscopic examination 2 months later, without any treatment.
Assuntos
Colite Ulcerativa/complicações , Pneumatose Cistoide Intestinal/complicações , Adulto , Humanos , Masculino , Pneumatose Cistoide Intestinal/patologiaRESUMO
BACKGROUND: Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission. METHODS: We conducted a multicenter, prospective, randomised-control trial of patients with remitting UC induced by granulocyte and monocyte adsorption apheresis or leukocytapheresis. Patients were randomly assigned to the apheresis group (twice per month for 12 months) or the control group (no apheresis treatment) using a 1:1 allocation ratio. The primary endpoint was the rate of cumulative clinical remission (Mayo score ≤ 2) at 12 months. The secondary endpoints were the rates of clinical remission, endoscopic remission, and complete endoscopic remission at 12 months. RESULTS: Between March 2013 and March 2017, 164 patients were enrolled. The cumulative remission rate at 12 months was 46.6% in the apheresis group and 36.4% in the control group (p = 0.1621). The rate of endoscopic remission at 12 months was significantly higher in the apheresis group than in the control group (42.5% vs. 25.9%) p = 0.0480). The rate of clinical remission (47.5% vs.32.1%, p = 0.0540) and complete endoscopic remission (33.8% vs.19.8%, p = 0.0513) tended to be higher in the apheresis than in the control group; however, the difference was not significant. No severe adverse events were observed in either group. CONCLUSIONS: Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12 months was comparable between the apheresis and control groups.
Assuntos
Colite Ulcerativa/terapia , Leucaférese , Indução de Remissão , Adulto , Colite Ulcerativa/diagnóstico por imagem , Colonoscopia , Feminino , Granulócitos , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: The new curcumin derivative Theracurmin® has a 27-fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn's disease. METHODS: In this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, nâ =â 20) or placebo (nâ =â 10) was administered to patients with active mild-to-moderate Crohn's disease for 12 weeks. The agent's efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. RESULTS: In the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (pâ =â 0.005). On intention-to-treat analysis, clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, which were significantly higher than those in the placebo group (all 0%; pâ =â 0.033, pâ =â 0.020, and pâ =â 0.020, respectively). Furthermore, reduction in endoscopic Crohn's disease severity (pâ =â 0.032) was observed at week 12 in the Theracurmin® group. The endoscopic remission rates were 15% and 0% in the Theracurmin® and placebo groups, respectively. Significant healing of anal lesions (pâ =â 0.017) was observed at week 8 in the Theracurmin® group. No serious adverse events were observed in either group throughout the study. CONCLUSIONS: Theracurmin® shows significant clinical and endoscopic efficacy together with a favorable safety profile in patients with active mild-to-moderate Crohn's disease. CLINICAL TRIAL UMIN REGISTRATION ID: UMIN000015770.
Assuntos
Doença de Crohn/tratamento farmacológico , Curcumina/farmacologia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Doença de Crohn/fisiopatologia , Curcumina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
We previously performed a randomized controlled trial (RCT) comparing targeted and random biopsy in neoplasia detection in patients with ulcerative colitis (UC), which showed the short-term effectiveness of targeted biopsy with one-time colonoscopy. In this retrospective cohort study, we investigated the long-term effectiveness of targeted biopsy in tertiary care hospitals, using the follow-up data from patients with UC for ≥ 8 years who had enrolled in the initial RCT. The primary outcome was death from colorectal cancer (CRC). Secondary outcomes were advanced neoplasia (CRC or high-grade dysplasia) and colectomy due to neoplasia after the RCT. We compared these outcomes between target and random groups. Data on 195 of the 221 patients (88.2%) enrolled in the previous RCT were collected from 28 institutions between 2008 and 2019. No patients died of CRC in either group, with a median 8.8-year follow-up demonstrating a robustness for targeted biopsy in terms of CRC death prevention. Advanced neoplasia was detected in four and three patients in the target and random groups, respectively. Colectomy was required due to neoplasia in three patients in each group. The chance of developing CRC in patients with a negative colonoscopy was low, and the targeted biopsy appeared effective in this population. Conversely, patients found with low-grade dysplasia at initial RCT have 10-fold higher risk of progression to high-grade dysplasia and/or CRC. Ten extracolonic malignancies were observed during the follow-up, resulting in four deaths. Panchromoendoscopy was used only in 4.6% and targeted biopsy was only performed in 59.1% of colonoscopies. We recommend targeted biopsy rather than > 33 random biopsies in real-world settings under adequate observation by specialists.
RESUMO
OBJECTIVES: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.