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2.
World J Gastroenterol ; 25(31): 4481-4492, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31496626

RESUMO

BACKGROUND: Ustekinumab was approved in Europe for the treatment of adults with moderate to severe Crohn's disease (CD) in 2016, and there is an urgent need for data on its everyday use. AIM: To obtain data on the daily use of ustekinumab. METHODS: This is a retrospective monocentric study. Patients with moderate to severe CD who began ustekinumab therapy at the inflammatory bowel diseases outpatient clinic of the Heidelberg University Hospital between December 2016 and March 2018 were selected based on electronic patient files. The primary study endpoint was combined steroid-free clinical remission or steroid-free clinical response at 24 ± 6 wk of ustekinumab therapy. Secondary study endpoints were: achievement of mucosal healing, sonographic and magnetic resonance imaging response, biochemical response, the need for intestinal surgery within 24 ± 6 wk after treatment initiation, the occurrence of adverse events, treatment discontinuation due to nonresponse or adverse events, improvement of extraintestinal manifestations, clinical response at 48 ± 6 wk of therapy, and association of response with nucleotid oligodimerisation domain 2 mutations. RESULTS: Fifty-seven patients with CD (5.3% anti-tumour necrosis factor α naïve, 63.2% having undergone at least one intestinal surgery) were included in the study. Twenty patients (35.1%) achieved steroid-free clinical remission, 6 (10.5%) steroid-free clinical response and 31 (54.4%) were non-responders. Treatment discontinuation due to adverse events occurred in two patients (3.5%). Male sex, the presence of extraintestinal manifestations and the use of steroids at baseline were predictors of nonresponse to ustekinumab therapy. CONCLUSION: In a "real-world" treatment-refractory cohort of patients with CD, ustekinumab appeared efficacious and safe.


Assuntos
Doença de Crohn/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Indução de Remissão/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/uso terapêutico , Adulto , Idoso , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Colonoscopia , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Esquema de Medicação , Resistência a Medicamentos , Feminino , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia , Ustekinumab/farmacologia , Adulto Jovem
3.
World J Gastroenterol ; 25(31): 4534-4554, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31496630

RESUMO

BACKGROUND: Crohn's disease (CD) can affect the entire gastrointestinal tract. Proximal small bowel (SB) lesions are associated with a significant risk of stricturing disease and multiple abdominal surgeries. The assessment of SB in patients with CD is therefore necessary because it may have a significant impact on prognosis with potential therapeutic implications. Because of the weak correlation that exists between symptoms and endoscopic disease activity, the "treat-to-target" paradigm has been developed, and the associated treatment goal is to achieve and maintain deep remission, encompassing both clinical and endoscopic remission. Small bowel capsule endoscopy (SBCE) allows to visualize the mucosal surface of the entire SB. At that time, there is no recommendation regarding the use of SBCE during follow-up. AIM: To investigate the impact of SBCE in a treat-to-target strategy in patients with CD. METHODS: An electronic literature search was conducted in PubMed and Cochrane library using the following search terms: "capsule endoscopy", in combination with "Crohn's disease" and "treat-to-target" or synonyms. Two authors independently reviewed titles and abstracts identified by the search strategy after duplicates were removed. Following the initial screening of abstracts, all articles containing information about SBCE in the context of treat-to-target strategy in patients with CD were included. Full-text articles were retrieved, reference lists were screened manually to identify additional studies. RESULTS: Forty-seven articles were included in this review. Two indexes are currently used to quantify disease activity using SBCE, and there is good correlation between them. SBCE was shown to be useful for disease reclassification in patients who are suspected of having or who are diagnosed with CD, with a significant incremental diagnostic yield compared to other diagnostic modalities. Nine studies also demonstrated that the mucosal healing can be evaluated by SBCE to monitor the effect of medical treatment in patients with CD. This review also demonstrated that SBCE can detect post-operative recurrence to a similar extent as ileocolonoscopy, and proximal SB lesions that are beyond the reach of the colonoscope in over half of the patients. CONCLUSION: SBCE could be incorporated in the treat-to-target algorithm for patients with CD. Randomized controlled trials are required to confirm its usefulness and reliability in this indication.


Assuntos
Endoscopia por Cápsula , Doença de Crohn/terapia , Íleo/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Jejuno/diagnóstico por imagem , Protocolos Clínicos , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Constrição Patológica/patologia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico por imagem , Humanos , Íleo/patologia , Mucosa Intestinal/patologia , Jejuno/patologia , Prognóstico , Recidiva , Reprodutibilidade dos Testes , Resultado do Tratamento
4.
World J Gastroenterol ; 25(31): 4555-4566, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31496631

RESUMO

BACKGROUND: Documentation of disease activity in patients affected by Crohn's disease (CD) is mandatory in order to manage patients properly. Magnetic resonance imaging (MRI) is considered the reference cross-sectional technique for the assessment of CD activity. Among MRI findings, layered pattern (LP) of contrast enhancement seems to be one of the most significant signs of severe disease activity; however, it has also been associated with chronic disease and mural fibrosis. AIM: To systematically evaluate the accuracy of LP of contrast enhancement in the diagnosis of active inflammation in patients with CD. METHODS: In February 2019, we searched the MEDLINE and Cochrane Central Register of Controlled Trials databases for studies evaluating the diagnostic accuracy of LP of contrast enhancement on MRI for the detection of active inflammation in patients with CD. To be included, studies had to use histopathologic analysis (endoscopy or surgery) as the reference standard. Risk of bias and applicability concerns of the included studies were evaluated by using items from the Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Pooled sensitivity and specificity were determined using a bivariate random-effect model. Heterogeneity was quantified by using the I 2 statistic. Our meta-analysis received no funding, and the review protocol was not published or registered in advance. RESULTS: Of the 1383 studies identified, five articles were finally selected for quantitative and qualitative synthesis (245 patients, 238 of whom had histopathologically confirmed CD, 144 with active inflammation and 94 with inactive disease). The meta-analysis showed a pooled sensitivity of 49.3% (95%CI: 41%-57.8%; I 2: 90.7%) and specificity of 89.1% (95%CI: 81.3%- 94.4%; I 2: 48.6%). Pooled PLR and NLR were 3.3 (95%CI: 1.9-5.7; I 2: 6.1%) and 0.6 (95%CI: 0.5-0.9; I 2 70.5%), respectively. SDOR was 6.8 (95%CI: 2.6-17.6; I 2: 27.1%). The summary ROC curve showed an area under the curve (AUC) of 0.82 (SE 0.06; Q* 0.76). High risk of bias and applicability concerns were observed in the domains of patient selection for one included study. CONCLUSION: LP on contrast-enhanced MRI is a specific finding to rule out active inflammation in patients with CD. Further studies using a prespecified definition of LP on contrast-enhanced MRI are needed to support our findings.


Assuntos
Meios de Contraste/administração & dosagem , Doença de Crohn/diagnóstico por imagem , Mucosa Intestinal/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Doença de Crohn/patologia , Humanos , Mucosa Intestinal/patologia , Imagem por Ressonância Magnética/instrumentação , Valor Preditivo dos Testes , Curva ROC
5.
World J Gastroenterol ; 25(30): 4148-4157, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435169

RESUMO

Patients with long-standing inflammatory bowel disease (IBD) involving at least 1/3 of the colon are at increased risk for colorectal cancer (CRC). Advancements in CRC screening and surveillance and improved treatment of IBD has reduced CRC incidence in patients with ulcerative colitis and Crohn's colitis. Most cases of CRC are thought to arise from dysplasia, and recent evidence suggests that the majority of dysplastic lesions in patients with IBD are visible, in part thanks to advancements in high definition colonoscopy and chromoendoscopy. Recent practice guidelines have supported the use of chromoendoscopy with targeted biopsies of visible lesions rather than traditional random biopsies. Endoscopists are encouraged to endoscopically resect visible dysplasia and only recommend surgery when a complete resection is not possible. New technologies such as virtual chromoendoscopy are emerging as potential tools in CRC screening. Patients with IBD at increased risk for developing CRC should undergo surveillance colonoscopy using new approaches and techniques.


Assuntos
Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/normas , Doenças Inflamatórias Intestinais/patologia , Lesões Pré-Cancerosas/patologia , Conduta Expectante/normas , Biópsia , Colonografia Tomográfica Computadorizada/métodos , Colonografia Tomográfica Computadorizada/normas , Colonoscopia/métodos , Colonoscopia/normas , Neoplasias Colorretais/patologia , Progressão da Doença , Detecção Precoce de Câncer/métodos , Ressecção Endoscópica de Mucosa/normas , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/cirurgia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/cirurgia
7.
Drug Dev Ind Pharm ; 45(11): 1799-1806, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31448962

RESUMO

A rapid, accurate, and sensitive reverse phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the estimation of Thymoquinone (TMQ) in API as well as in noisome. The chromatograms were developed with the mobile phase - water: 2-propanol: methanol (50:45:5 v/v/v) as a solvent system at 254 nm. The method was validated as per ICH guidelines for different parameters and the recovery of TMQ was calculated in developed niosomes. Further, TMQ loaded niosomes (TMQNIOS) were prepared and evaluated for different parameters. The optimized TMQNIOS (F3) was further evaluated for surface morphology, in vitro drug release, permeation study, and confocal laser scanning microscopic (CLSM) study. The method showed linearity range between 6.25 and 100 µg/ml with low detection limit and quantitation limit with a value of 2.08 and 6.25 µg/ml. The developed formulations showed the vesicle size and encapsulation efficiency in the range of 157.32 ± 3.15 to 211.44 ± 5.23 nm and 59.32 ± 4.87 to 83.21 ± 3.55%, respectively. The drug release result showed the significant higher release from TMQNIOS in compared to TMQDIS, and the release kinetics data showed Higuchi's equation with highest regression coefficient values. The permeation study and the confocal laser microscopy study further confirmed the enhancement in permeation of TMQ in the intestinal mucosa.


Assuntos
Benzoquinonas/análise , Benzoquinonas/farmacocinética , Química Farmacêutica/métodos , Animais , Benzoquinonas/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Composição de Medicamentos , Liberação Controlada de Fármacos , Cabras , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/metabolismo , Lipossomos , Microscopia Confocal , Tamanho da Partícula , Permeabilidade
8.
J Drugs Dermatol ; 18(8): 832-834, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424717

RESUMO

INTRODUCTION: While psoriasis, psoriatic arthritis, and Crohn's Disease (CD) all share a common central pathogenesis pathway and a wide overlap of treatment regime, discrepancies still exist and are highlighted by the variability in the effectiveness of certain immunomodulating agents. Etanercept, for example, has been shown to be ineffective in CD due to its inability to induce T-cell apoptosis in the intestinal mucosa. CASE: We describe the case of a 37-year-old man with a 20-year history of psoriatic arthritis. The patient presented with abdominal pain, watery diarrhea with mild hematochezia, and a reported 24-pound unintentional weight loss over the past five months. Of note, the patient began treatment with etanercept five months earlier after discontinuation of infliximab for his psoriatic arthritis symptoms. Colonoscopy with terminal ileum intubation revealed active colitis and intestinal biopsy results showed marked ulcerations and non-caseating granulomas, indicative of CD. Etanercept was subsequently discontinued and the patient was started on ustekinumab, leading to remission of both his psoriatic arthritis and new onset CD. DISCUSSION: Because the concurrent existence of psoriatic arthritis and IBD is becoming increasingly appreciated in recent literature, healthcare providers should have a high index of suspicion in patients with psoriasis and psoriatic arthritis presenting with unusual intestinal symptoms. Etanercept is intestinally inactive and should be used in caution in patients with psoriasis and psoriatic arthritis, as it may unmask underlying CD in this predisposed patient population. Dermatologists should also be aware of recent studies suggesting that etanercept directly contributes to the development of CD by altering the inflammatory cytokine milieu. Lastly, ustekinumab was successful in relieving our patient's cutaneous, joint, and gastrointestinal symptoms and may be considered an effective treatment option in patients suffering from both psoriasis and CD or the paradoxical induction of one disease entity secondary to treatment of the other.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Doença de Crohn/induzido quimicamente , Etanercepte/efeitos adversos , Adulto , Biópsia , Colonoscopia , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino
9.
Ann Nucl Med ; 33(10): 740-745, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31297700

RESUMO

OBJECTIVE: On hepatobiliary scintigraphy, "preferential gallbladder (GB) filling without tracer excretion into the small bowel (SB) [p-GB-no-SB]" is occasionally seen on images obtained up to an hour. In such cases, many practitioners administer cholecystokinin (CCK) (even when the measurement of GB ejection fraction is not indicated) or obtain delayed images (DI) to exclude common bile duct (CBD) obstruction. We aimed (1) to assess the prevalence of clinically relevant CBD obstruction found by CCK administration or DI in this circumstance and (2) to find imaging findings and/or parameters that can be used to triage patients who do or do not need such maneuvers. METHODS: Of 1244 scans reviewed, 1089 were excluded because of one or more of the following reasons: SB visualized within 60 min, GB not visualized within 60 min, severely decreased hepatic function, and less than 1 month of clinical follow-up after scanning. The remaining 155 showed p-GB-no-SB with clinical follow-up available for ≥ 1 month. For the 155 scans, clearance of liver parenchymal activity was assessed. RESULTS: Of the 155 scans, 142 showed visually prompt clearance of liver parenchymal activity (group A), while 13 scans showed mild to moderately delayed clearance of liver parenchymal activity with or without initial decreased hepatic uptake (group B). 134 of 142 in group A had additional imaging (99 CCK or 35 DI); all 134 showed SB visualization. Eight remaining scans were terminated without additional imaging. None of the 142 had any event attributable to CBD obstruction on follow-up. All 13 in group B had additional imaging (9 CCK, 4 DI); SB visualized in 11, but not in two; clinical follow-up revealed no CBD obstruction in 11. ERCP revealed CBD obstruction in the latter two. CONCLUSIONS: When a HIDA scan shows p-GB-no-SB, the probability of identifying clinically relevant CBD obstruction by additional imaging with CCK or DI is virtually zero in an acute clinical setting if clearance of liver parenchymal activity is prompt. Additional imaging with CCK or DI can be reserved for only those showing abnormal clearance of liver parenchymal activity.


Assuntos
Colecistocinina/administração & dosagem , Colecistocinina/farmacologia , Vesícula Biliar/efeitos dos fármacos , Vesícula Biliar/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Vesícula Biliar/diagnóstico por imagem , Humanos , Mucosa Intestinal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Traçadores Radioativos , Cintilografia , Estudos Retrospectivos , Lidofenina Tecnécio Tc 99m/farmacocinética , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacos
11.
Gastroenterology ; 157(4): 1007-1018.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279871

RESUMO

BACKGROUND & AIMS: Vedolizumab is a gut-selective monoclonal antibody for the treatment of moderately to severely active Crohn's disease (CD). We performed a prospective study of endoscopic, radiologic, and histologic healing in patients with CD who received vedolizumab therapy. METHODS: We performed a phase 3b, open-label, single-group study of 101 patients with at least 3 months of active CD (a CD Activity Index [CDAI] score of 220-450, a simple endoscopic score for CD [SES-CD] of 7 or more, 1 or more mucosal ulcerations [identified by endoscopy], and failure of conventional therapy) from March 2015 through December 2017. Among the patients enrolled, 54.5% had previous failure of 1 or more tumor necrosis factor (TNF) antagonists and 44.6% had severe endoscopic disease activity (SES-CD scores above 15) at baseline. Participants received vedolizumab (300 mg intravenously) at weeks 0, 2, and 6, and then every 8 weeks thereafter, for 26 weeks (primary study) or 52 weeks (substudy, 56 patients). The primary endpoint at week 26 was endoscopic remission (SES-CD score of 4 or less); other endpoints included endoscopic response (50% reduction in SES-CD), radiologic remission (magnetic resonance index of activity score below 7), and histologic response (modified global histologic disease activity score of 4 or less). RESULTS: At week 26, 11.9% of patients were in endoscopic remission (95% confidence interval [CI] 6.3-9.8); at week 52, 17.9% of the patients were in endoscopic remission (95% CI 8.9-30.4). Higher proportions of patients naïve to TNF antagonists achieved endoscopic remission than patients with TNF-antagonist-failure at weeks 26 and 52. Higher proportion of patients with moderate CD (SES-CD scores, 7-15) achieved endoscopic remission at weeks 26 and 52 than patients with severe CD (SES-CD scores above 15). The proportion of patients with complete mucosal healing increased over time, with greater rates of healing in the colon than in the ileum. Remission was detected by magnetic resonance enterography in 21.9% of patients at week 26 (95% CI 9.3-40.0) and in 38.1% at week 52 (95% CI 18.1-61.6). At week 26, 24.4% of patients had a histologic response in the colon (95% CI 15.3-35.4) and 28.3% of patients had a histologic response in the ileum (95% CI 17.5-41.4). At week 52, 20.5% of patients had a histologic response in the colon (95% CI 9.8-35.3) and 34.3% of patients had a histologic response in the ileum (95% CI 19.1-52.2). There were no notable safety issues, including worsening of extraintestinal manifestations. CONCLUSIONS: In a phase 3b trial, we found that 26 and 52 weeks of treatment with vedolizumab (300 mg, at weeks 0, 2, and 6, and then every 8 weeks thereafter) induces endoscopic, radiologic, and histologic healing in patients with moderately to severely active CD. ClinicalTrials.gov no: NCT02425111.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Endoscopia Gastrointestinal , Fármacos Gastrointestinais/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Imagem por Ressonância Magnética , Cicatrização/efeitos dos fármacos , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biópsia , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/patologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
World J Gastroenterol ; 25(26): 3344-3358, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341360

RESUMO

Gastroduodenal disease (GDD) was initially thought to be uncommon in Africa. Amongst others, lack of access to optimal health infrastructure and suspicion of conventional medicine resulted in the reported prevalence of GDD being significantly lower than that in other areas of the world. Following the increasing availability of flexible upper gastro-intestinal endoscopy, it has now become apparent that GDD, especially peptic ulcer disease (PUD), is prevalent across the continent of Africa. Recognised risk factors for gastric cancer (GCA) include Helicobater pylori (H. pylori), diet, Epstein-Barr virus infection and industrial chemical exposure, while those for PUD are H. pylori, non-steroidal anti-inflammatory drug (NSAID)-use, smoking and alcohol consumption. Of these, H. pylori is generally accepted to be causally related to the development of atrophic gastritis (AG), intestinal metaplasia (IM), PUD and distal GCA. Here, we perform a systematic review of the patterns of GDD across Africa obtained with endoscopy, and complement the analysis with new data obtained on pre-malignant gastric his-topathological lesions in Accra, Ghana which was compared with previous data from Maputo, Mozambique. As there is a general lack of structured cohort studies in Africa, we also considered endoscopy-based hospital or tertiary centre studies of symptomatic individuals. In Africa, there is considerable heterogeneity in the prevalence of PUD with no clear geographical patterns. Furthermore, there are differences in PUD within-country despite universally endemic H. pylori infection. PUD is not uncommon in Africa. Most of the African tertiary-centre studies had higher prevalence of PUD when compared with similar studies in western countries. An additional intriguing observation is a recent, ongoing decline in PUD in some African countries where H. pylori infection is still high. One possible reason for the high, sustained prevalence of PUD may be the significant use of NSAIDs in local or over-the-counter preparations. The prevalence of AG and IM, were similar or modestly higher over rates in western countries but lower than those seen in Asia. . In our new data, sampling of 136 patients in Accra detected evidence of pre-malignant lesions (AG and/or IM) in 20 individuals (14.7%). Likewise, the prevalence of pre-malignant lesions, in a sample of 109 patients from Maputo, were 8.3% AG and 8.3% IM. While H. pylori is endemic in Africa, the observed prevalence for GCA is rather low. However, cancer data is drawn from country cancer registries that are not comprehensive due to considerable variation in the availability of efficient local cancer reporting systems, diagnostic health facilities and expertise. Validation of cases and their source as well as specificity of outcome definitions are not explicit in most studies further contributing to uncertainty about the precise incidence rates of GCA on the continent. We conclude that evidence is still lacking to support (or not) the African enigma theory due to inconsistencies in the data that indicate a particularly low incidence of GDD in African countries.


Assuntos
Gastrite Atrófica/epidemiologia , Infecções por Helicobacter/epidemiologia , Úlcera Péptica/epidemiologia , Neoplasias Gástricas/epidemiologia , Endoscopia Gastrointestinal , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/etiologia , Gana/epidemiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/etiologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Metaplasia , Úlcera Péptica/diagnóstico , Úlcera Péptica/etiologia , Prevalência , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiologia
14.
Pharmacology ; 104(1-2): 51-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31067545

RESUMO

Mesalazine is the gold standard drug for treatment of ulcerative colitis (UC). Here, we describe 4 cases of familial adenomatous polyposis (FAP) patients with UC that showed reduction of intestinal polyp diameter by mesalazine treatment. Of note, the effects of mesalazine on the development of intestinal polyps in FAP patients have not been reported, and we further investigated whether the short-term use of high-dose mesalazine (4 g/day) has harmful effects on FAP patients or not. The authors found that the treatment showed slightly adverse events in FAP patients. However, mesalazine tended to reduce the number of colon polyps in male subjects with FAP. This report provides basic information for planning a double-blind, randomized, clinical trial that aims to show mesalazine's potential to suppress intestinal polyp development in FAP.


Assuntos
Polipose Adenomatosa do Colo/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Mesalamina/administração & dosagem , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/patologia , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Colo/diagnóstico por imagem , Colo/efeitos dos fármacos , Colo/patologia , Colonoscopia , Relação Dose-Resposta a Droga , Seguimentos , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Mesalamina/efeitos adversos , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
15.
World J Gastroenterol ; 25(16): 1928-1935, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31086461

RESUMO

Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis (UC), atypical UC, Crohn's disease (CD) and IBD unclassified. Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid (non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD, is histologically characterized by increased intraepithelial lymphocytes (> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis, villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.


Assuntos
Duodenite/diagnóstico , Esofagite/diagnóstico , Gastrite/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Trato Gastrointestinal Superior/patologia , Criança , Diagnóstico Diferencial , Duodenite/imunologia , Duodenite/patologia , Endoscopia Gastrointestinal , Esofagite/imunologia , Esofagite/patologia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Gastrite/imunologia , Gastrite/patologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Linfócitos Intraepiteliais/imunologia , Trato Gastrointestinal Superior/diagnóstico por imagem , Trato Gastrointestinal Superior/imunologia
16.
J Surg Res ; 242: 111-117, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31075655

RESUMO

BACKGROUND: Mucosal appendicitis is a controversial entity that is histologically distinct from transmural appendicitis. There is mixed opinion regarding mucosal inflammation as a spectrum of appendicitis versus a negative appendectomy. The ability to distinguish these diagnoses preoperatively is of importance to prevent unnecessary surgery. We hypothesize that patients with mucosal appendicitis can be discriminated from those with transmural disease based on specific preoperative clinical and imaging findings. MATERIALS AND METHODS: After IRB approval, all patients who underwent laparoscopic appendectomy at our institution during 2015 were reviewed in the electronic medical record. Patients with mucosal appendicitis were identified and matched 2:1 to a random cohort of nonperforated transmural appendicitis cases. Demographic and clinical data were collected, including history, examination, laboratory, and imaging findings. Preoperative factors associated with mucosal appendicitis were modeled using binomial logistic regression analysis. RESULTS: Of 1153 appendectomies performed during 2015, 103 patients had pathologic diagnosis of mucosal appendicitis. When compared with patients with mucosal infection, leukocytosis >10,000 per microliter led to 5.9 times higher likelihood of transmural pathology (P = 0.000). Noncompressibility on ultrasound was associated with 7.3 times higher likelihood of transmural disease (P = 0.015). Echogenic changes were predictive of transmural appendicitis, conferring 3.9 times the risk (P = 0.007). Presence of free fluid led to 2.3 times the rate of transmural pathology (P = 0.007). Finally, for every millimeter decrease in appendiceal diameter, patients were half as likely to exhibit transmural disease (P = 0.000). Together, these variables can successfully predict presence of mucosal appendicitis on final pathology report at a rate of 82.1%, and explain 60% of the variance in diagnosis of mucosal versus transmural appendicitis (P = 0.000). CONCLUSIONS: Mucosal appendicitis remains a controversial pathologic entity, but is not associated with greater complications compared with transmural appendicitis when treated with laparoscopic appendectomy. Transmural disease can be predicted by leukocytosis, noncompressible appendix, presence of free fluid, larger appendiceal diameter and echogenicity.


Assuntos
Apendicite/diagnóstico , Apêndice/diagnóstico por imagem , Mucosa Intestinal/patologia , Leucocitose/diagnóstico , Adolescente , Apendicectomia/efeitos adversos , Apendicectomia/estatística & dados numéricos , Apendicite/complicações , Apendicite/cirurgia , Apêndice/patologia , Apêndice/cirurgia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/estatística & dados numéricos , Contagem de Leucócitos , Leucocitose/sangue , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Estudos Retrospectivos , Ultrassonografia
17.
Gastrointest Endosc Clin N Am ; 29(3): 471-485, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078248

RESUMO

Capsule endoscopy (CE) provides visualization of small bowel mucosa for evidence of inflammation. Given its ability to detect subtle mucosal changes, CE is recommended in the diagnostic work-up of small bowel Crohn disease (CD) and also in monitoring mucosal response to therapy in nonstricturing CD. Patency capsule and cross-sectional imaging can reduce risk of capsule retention in patients with suspected stenotic disease. CE is complementary to magnetic resonance enterography, which can provide extraintestinal information. Device-assisted enteroscopy has limited role in CD.


Assuntos
Enteroscopia de Balão/métodos , Endoscopia por Cápsula/métodos , Doença de Crohn/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Radiologistas/psicologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Papel do Médico
19.
BMC Cancer ; 19(1): 428, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072353

RESUMO

BACKGROUND: Colorectal cancer remains the second leading cause of cancer death in the United States, and increased risk in patients with ulcerative colitis (a subset of inflammatory bowel disease) has motivated studies into early markers of dysplasia. The development of clinically translatable multiphoton imaging systems has allowed for the potential of in vivo label-free imaging of epithelial crypt structures via autofluorescence and/or second harmonic generation (SHG). SHG has been used to investigate collagen structures in various types of cancer, though the changes that colorectal epithelial collagen structures undergo during tumor development, specifically colitis-associated tumors, have not been fully investigated. METHODS: This study used two murine models, using A/J mice, one for spontaneous carcinoma and one for colitis-associated carcinoma, to investigate and quantify SHG image features that could potentially inform future study designs of endoscopic multiphoton imaging systems. The spontaneous tumor model comprised a series of six weekly injections of azoxymethane (AOM model). The colitis-associated tumor model comprised a single injection of AOM, followed by cycles of drinking water with dissolved dextran sodium sulfate salt (AOM-DSS model). SHG images of freshly resected murine colon were acquired with a multiphoton imaging system, and image features, such as crypt size, shape and distribution, were quantified using an automated algorithm. RESULTS: The comparison of quantified features of crypt morphology demonstrated the ability of our quantitative image feature algorithms to detect differences between spontaneous (AOM model) and colitis-associated (AOM-DSS model) murine colorectal tissue specimens. There were statistically significant differences in the mean and standard deviation of nearest neighbor (distance between crypts) and circularity between the Control cohort, AOM and AOM-DSS cohorts. We also saw significance between AOM and AOM-DSS cohorts when calculating nearest neighbor in images acquired at fixed depths. CONCLUSION: The results provide insight into the ability of SHG imaging to yield relevant data about the crypt microstructure in colorectal epithelium, specifically the potential to distinguish between spontaneous and colitis-associated murine models using quantification of crypt shape and distribution, informing future design of translational multiphoton imaging systems and protocols.


Assuntos
Colite/patologia , Colo/patologia , Neoplasias do Colo/diagnóstico por imagem , Mucosa Intestinal/patologia , Microscopia de Geração do Segundo Harmônico , Animais , Colite/induzido quimicamente , Colite/diagnóstico por imagem , Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Progressão da Doença , Humanos , Mucosa Intestinal/diagnóstico por imagem , Camundongos
20.
Int J Surg Pathol ; 27(6): 643-646, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31046499

RESUMO

Mastocytosis is a rare and heterogeneous group of disorders that may be limited to the skin and even spontaneously regress or may have a systemic presentation with multi-organ involvement and poor outcome. Among the extracutaneous sites, gastrointestinal tract is often affected, but nonspecific clinical manifestations combined with subtle histological findings of the disease makes the diagnosis of gastrointestinal mastocytosis rather hard. In absence of a high index of suspicion, gastrointestinal involvement is easily overlooked. We report a challenging case of systemic mastocytosis presenting with isolated gastrointestinal manifestations without skin involvement, in which the diagnosis was missed at first evaluation of intestinal biopsies.


Assuntos
Medula Óssea/patologia , Neoplasias do Íleo/diagnóstico , Íleo/patologia , Mucosa Intestinal/patologia , Mastocitose Sistêmica/diagnóstico , Idoso , Antineoplásicos/uso terapêutico , Biópsia , Endoscopia Gastrointestinal , Humanos , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Íleo/patologia , Íleo/diagnóstico por imagem , Mucosa Intestinal/citologia , Mucosa Intestinal/diagnóstico por imagem , Masculino , Mastócitos/patologia , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/patologia , Resultado do Tratamento
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