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1.
N Engl J Med ; 389(19): 1790-1796, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37937778

RESUMO

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.


Assuntos
Gastroenterite , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Lactente , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Enterite/induzido quimicamente , Enterite/diagnóstico , Enterite/tratamento farmacológico , Enterite/imunologia , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Insuficiência de Crescimento/induzido quimicamente , Insuficiência de Crescimento/imunologia , Diarreia Infantil/induzido quimicamente , Diarreia Infantil/imunologia , Gastroenterite/induzido quimicamente , Gastroenterite/diagnóstico , Gastroenterite/tratamento farmacológico , Gastroenterite/imunologia , Enterocolite/induzido quimicamente , Enterocolite/diagnóstico , Enterocolite/tratamento farmacológico , Enterocolite/imunologia , Receptor de Morte Celular Programada 1/imunologia
2.
J Immunother Cancer ; 11(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37349130

RESUMO

PURPOSE: Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-related enterocolitis (irEC). We examined the effect of resumption of ICIs with or without concurrent selective immunosuppressive therapy (SIT) on rates of symptom recurrence and survival outcomes. METHODS: This retrospective, multicenter study examined patients who were treated with ICI and developed irEC requiring SIT (infliximab or vedolizumab) for initial symptom control or to facilitate steroid tapering between May 2015 and June 2020. After symptom resolution, patients were restarted either on ICI alone or on concurrent ICI and SIT at the discretion of the treating physicians. The associations between irEC recurrence and treatment group were assessed via univariate analyses and multivariate logistic regression. Cox proportional hazards model was used for survival analysis. RESULTS: Of the 138 included patients who required SIT for initial irEC symptom control, 61 (44.2%) patients resumed ICI without concurrent SIT (control group) and 77 (55.8%) patients resumed ICI therapy with concurrent SIT: 33 with infliximab and 44 with vedolizumab. After symptom resolution, patients in the control group were more commonly restarted on a different ICI regimen (65.6%) compared with those receiving SIT (31.2%) (p<0.001). The total number of ICI doses administered after irEC resolution and ICI resumption was similar in both groups (four to five doses). Recurrence of severe colitis or diarrhea after ICI resumption was seen in 34.4% of controls compared with 20.8% of patients receiving concurrent SIT. Concurrent SIT was associated with reduced risk of severe irEC recurrence after ICI resumption in a multivariate logistic regression model (OR 0.34; 95% CI 0.13 to 0.92; p=0.034). There was no difference in survival outcomes between patients in the control group and patients concurrently treated with SIT. CONCLUSION: After resolution of irEC symptoms, reinitiation of ICI with concurrent SIT is safe, reduces severe irEC recurrence, and has no negative impact on survival outcomes.


Assuntos
Antineoplásicos Imunológicos , Enterocolite , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Infliximab/uso terapêutico , Estudos Retrospectivos , Antineoplásicos Imunológicos/efeitos adversos , Enterocolite/tratamento farmacológico , Terapia de Imunossupressão
3.
Cancer ; 129(3): 367-375, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377339

RESUMO

BACKGROUND: Gastrointestinal immune-related adverse events are frequently caused by immune checkpoint inhibitors (ICIs) and often require interruption of cancer treatment. Compared with ICI colitis and enteritis, limited information exists about ICI gastritis. This study characterized clinical features and treatment outcomes of ICI gastritis. METHODS: Consecutive cancer patients who received ICIs and underwent endoscopy with gastric biopsies while on ICIs from 2011 to 2021 were retrospectively assessed. Specific histopathologic features identified ICI gastritis. RESULTS: Of 6450 ICI-treated patients, 162 (2.5%) underwent endoscopy with gastric biopsies. ICI gastritis was identified in 54 (33%) biopsied patients; 38 (70%) had concurrent ICI enteritis/colitis and 16 (30%) had isolated ICI gastritis. Dyspepsia (38%) and bloating (25%) were the most frequent symptoms of isolated ICI gastritis. Compared with patients with concomitant enteritis/colitis, patients with isolated gastritis were less likely to have diarrhea (13% vs 68%; p < .001) or abdominal pain (19% vs 47%; p = .07). Patients with isolated ICI gastritis less frequently required glucocorticoids (69% vs 92%; p = .04) and had lower incidence of ICI hold/withdrawal (13% vs 42%; p = .06). There was no association between severity or extent of luminal inflammation and antitumor response (p = .85 and p = .44, respectively). Endoscopically, gastric mucosa appeared normal in 11 (20%) patients with biopsy-proven ICI gastritis. CONCLUSION: ICI gastritis may present alone or more commonly with concurrent enteritis/colitis, which may differentiate its clinical course. Gastric biopsies are required to diagnose a substantial minority of endoscopically normal, clinically significant cases. Most patients with isolated gastritis can continue ICI therapy uninterrupted, but a notable proportion require glucocorticoids. PLAIN LANGUAGE SUMMARY: Immune checkpoint inhibitors are effective anticancer treatments, but can cause inflammatory toxicities, including of the stomach (gastritis), intestine, and colon. Limited information is available on gastritis triggered by these agents. Adult patients with cancer who were treated with immune checkpoint inhibitors and had an upper gastrointestinal endoscopy with biopsies of the stomach were examined. More than two-thirds (70%) of people with checkpoint inhibitor gastritis also had inflammatory changes of the small intestine and/or colon. Compared with patients with isolated checkpoint gastritis, the subgroup with concomitant enteritis/colitis more frequently had abdominal pain, diarrhea, needed steroids, and/or needed to pause or stop antitumor therapy.


Assuntos
Antineoplásicos Imunológicos , Colite , Enterocolite , Gastrite , Neoplasias , Adulto , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Antineoplásicos Imunológicos/uso terapêutico , Gastrite/complicações , Gastrite/tratamento farmacológico , Gastrite/diagnóstico , Enterocolite/induzido quimicamente , Enterocolite/tratamento farmacológico , Neoplasias/tratamento farmacológico , Colite/induzido quimicamente , Diarreia/induzido quimicamente , Glucocorticoides/uso terapêutico , Dor Abdominal/induzido quimicamente , Dor Abdominal/tratamento farmacológico , Progressão da Doença
4.
Pharmacogenomics ; 23(18): 953-959, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382550

RESUMO

Capecitabine is a widely-used antineoplastic drug, a prodrug to 5-fluorouracil which commonly induces gastrointestinal toxicity. Enterocolitis, as a rarely recognized gastrointestinal adverse effect (AE) of capecitabine, is potentially severe and usually results in antitumor treatment withdrawal. For the better management of severe AEs, pharmacogenetics is one promising field. Herein, we describe a case of capecitabine-induced enterocolitis presenting with severe diarrhea in order to improve recognition by clinicians. Moreover, we conduct a pharmacogenetic profile of the patient and review the current studies of gene polymorphisms of 5-fluorouracil-related diarrhea, hoping to offer a reference for further clinical pharmacogenetic practice in predicting capecitabine AEs showing diarrhea as the main symptom.


Assuntos
Enterocolite , Farmacogenética , Humanos , Capecitabina/efeitos adversos , Fluoruracila/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Enterocolite/induzido quimicamente , Enterocolite/tratamento farmacológico , Enterocolite/genética
5.
Rev Chilena Infectol ; 39(1): 59-69, 2022 02.
Artigo em Espanhol | MEDLINE | ID: mdl-35735281

RESUMO

Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.


Assuntos
Antineoplásicos , Enterocolite Neutropênica , Enterocolite , Neoplasias , Neutropenia , Antineoplásicos/uso terapêutico , Criança , Enterocolite/complicações , Enterocolite/diagnóstico , Enterocolite/tratamento farmacológico , Enterocolite Neutropênica/diagnóstico , Enterocolite Neutropênica/tratamento farmacológico , Enterocolite Neutropênica/etiologia , Humanos , Hospedeiro Imunocomprometido , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/complicações
6.
Rev Esp Enferm Dig ; 114(7): 435-436, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35187938

RESUMO

Cytomegalovirus (CMV) infection is very common in immunosuppressed patients. It can y puede afectar a todo el tracto gastrointestinal, presentándose como úlceras o pseudotumores. A 43-year-old male with no personal background of interest, was studied due to constitutional syndrome. The diagnosis was neoplasia of the right colon, reported by colonoscopy and CT scan. A right hemicolectomy was performed with oncologic character. The definitive histology was CMV infectious colitis with positive immunohistochemical staining. Treatment with ganciclovir was started and the patient was diagnosed with HIV infection. The unusual finding of CMV infection as a pseudotumor can simulate, clinically and radiologically, a colonic neoplasm. It has been described in the literature in patients immunocompromised by HIV; however, the absence of risk factors means that it can be confused with a primary neoformative process.


Assuntos
Colite , Neoplasias do Colo , Infecções por Citomegalovirus , Enterocolite , Infecções por HIV , Adulto , Antivirais/uso terapêutico , Colite/diagnóstico por imagem , Colo/patologia , Neoplasias do Colo/complicações , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Enterocolite/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino
7.
Rev. chil. infectol ; 39(1): 59-69, feb. 2022. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1388333

RESUMO

Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.


Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.


Assuntos
Humanos , Criança , Enterocolite Neutropênica/diagnóstico , Enterocolite Neutropênica/etiologia , Enterocolite Neutropênica/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/complicações , Antineoplásicos/uso terapêutico , Hospedeiro Imunocomprometido , Enterocolite/complicações , Enterocolite/diagnóstico , Enterocolite/tratamento farmacológico
8.
Biomolecules ; 13(1)2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36671455

RESUMO

The progressively rising food-borne Campylobacter jejuni infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both C. jejuni virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10-/- mice received synthetic DESF via the drinking water starting seven days before oral infection with C. jejuni strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in C. jejuni infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute C. jejuni induced enterocolitis.


Assuntos
Infecções por Campylobacter , Campylobacter jejuni , Enterocolite , Animais , Camundongos , Desferroxamina/farmacologia , Desferroxamina/uso terapêutico , Infecções por Campylobacter/tratamento farmacológico , Enterocolite/tratamento farmacológico , Intestinos
9.
Pediatr Surg Int ; 37(10): 1467-1472, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309717

RESUMO

INTRODUCTION: Stasis from obstruction at the level of the internal anal sphincter (IAS) can lead to Hirschsprung-associated enterocolitis (HAEC) and may be improved by botulinum toxin (BT) injections. Our aim was to determine if BT injection during HAEC episodes decreased the number of recurrent HAEC episodes and/or increased the interval between readmissions. METHODS: A retrospective review was performed of patients admitted for HAEC from January 2010 to December 2019. Demographics and outcomes of patients who received BT were compared to patients who did not receive BT during their hospital stay. RESULTS: A total of 120 episodes of HAEC occurred in 40 patients; 30 patients (75%) were male, 7 (18%) had Trisomy 21 and 10 (25%) had long-segment disease. On multivariate analysis, patients who received BT during their inpatient HAEC episode had a longer median time between readmissions (p = 0.04) and trending toward an association with fewer readmissions prior to a follow-up clinic visit (p = 0.08). CONCLUSION: The use of BT in HD patients hospitalized for HAEC is associated with an increased time between recurrent HAEC episodes and trended toward fewer recurrent episodes. The use of BT should be considered in the management of patients admitted with HAEC.


Assuntos
Enterocolite , Doença de Hirschsprung , Criança , Criança Hospitalizada , Enterocolite/tratamento farmacológico , Enterocolite/epidemiologia , Doença de Hirschsprung/complicações , Doença de Hirschsprung/tratamento farmacológico , Humanos , Lactente , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos
10.
Ital J Pediatr ; 47(1): 149, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215305

RESUMO

BACKGROUND: Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available. We herein present for the first time longitudinal assessment of bowel morphology in a GSD Ib child suffering from Crohn disease-like enterocolitis treated with empagliflozin. CASE PRESENTATION: A 14-year-old boy with GSD Ib and severe IBD was (off-label) treated with empagliflozin (20 mg/day) after informed oral and written consent was obtained from the patient's parents. No adverse events were noted. Clinical symptoms and stool frequency improved within the first week of treatment. Pediatric Crohn disease activity index (PCDAI) normalised within the first month of treatment. Abdomen magnetic resonance imaging (MRI) performed 3 months after treatment initiation showed dramatic decrease in disease activity and length. Similar findings were reported on histology at 5.5 months. At 7.5 months hemoglobin levels normalised and fecal calprotectin almost normalised. Improved neutrophil count, metabolic control and quality of life were also noted. G-CSF dose was decreased by 33% and the patient was partly weaned from tube feeding. CONCLUSIONS: This is the first report presenting extensive gastrointestinal morphology follow-up in a GSD Ib patient receiving empagliflozin. The present case suggests that empagliflozin can be safe and effective in inducing IBD remission in GSD Ib patients and can even postpone surgery. Future studies are required to confirm its effect over time and assess its benefit in various disease stages. The development of an international collaborating networks for systematic data collection is worthy.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Enterocolite/tratamento farmacológico , Glucosídeos/uso terapêutico , Doença de Depósito de Glicogênio Tipo I/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adolescente , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Indução de Remissão
11.
BMC Infect Dis ; 21(1): 530, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090366

RESUMO

BACKGROUND: Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection. CASE PRESENTATION: A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient's coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV. CONCLUSIONS: We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.


Assuntos
Infecções por Citomegalovirus/complicações , Enterocolite/tratamento farmacológico , Ganciclovir/uso terapêutico , Rivaroxabana/uso terapêutico , Trombose/diagnóstico , Proteína ADAMTS13/metabolismo , Idoso , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Enterocolite/complicações , Enterocolite/virologia , Humanos , Perfuração Intestinal/cirurgia , Masculino , Testes Sorológicos , Trombose/complicações
12.
Am J Gastroenterol ; 116(1): 188-197, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065587

RESUMO

INTRODUCTION: To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). METHODS: All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. RESULTS: During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. Of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P ≤ 0.0001), transplanted more frequently due to biliary atresia (P ≤ 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P ≤ 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. DISCUSSION: EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.


Assuntos
Enterite/epidemiologia , Enterocolite/epidemiologia , Eosinofilia/epidemiologia , Esofagite Eosinofílica/epidemiologia , Gastrite/epidemiologia , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Antialérgicos/uso terapêutico , Atresia Biliar/cirurgia , Budesonida/uso terapêutico , Criança , Pré-Escolar , Colestase Intra-Hepática/cirurgia , Dermatite Atópica/epidemiologia , Progressão da Doença , Redução da Medicação , Enterite/tratamento farmacológico , Enterite/fisiopatologia , Enterocolite/tratamento farmacológico , Enterocolite/fisiopatologia , Eosinofilia/tratamento farmacológico , Eosinofilia/fisiopatologia , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/fisiopatologia , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Seguimentos , Gastrite/tratamento farmacológico , Gastrite/fisiopatologia , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Humanos , Hipersensibilidade/epidemiologia , Imunossupressores/uso terapêutico , Lactente , Cetotifeno/uso terapêutico , Falência Hepática Aguda/cirurgia , Transtornos Linfoproliferativos/epidemiologia , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/fisiopatologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tacrolimo/uso terapêutico , Resultado do Tratamento , Viremia/epidemiologia
13.
Rev Esp Enferm Dig ; 112(11): 889-890, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33054275

RESUMO

Immunotherapy is gaining significance in the management of oncological disease. It has demonstrated high levels of efficacy, though it also has hitherto unknown side effects, such as colitis. We present the first case of immune checkpoint inhibitor colitis (nivolumab+ipilimumab) refractory to corticoids treated in our hospital.


Assuntos
Colite , Enterocolite , Colite/induzido quimicamente , Enterocolite/induzido quimicamente , Enterocolite/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , Ipilimumab/efeitos adversos , Nivolumabe/efeitos adversos
14.
J Immunother Cancer ; 8(2)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33033184

RESUMO

BACKGROUND AND AIMS: Immune checkpoint inhibitor (ICI) enterocolitis is a common immune-related adverse event and can be fatal, especially when not diagnosed and treated promptly. The current gold standard for diagnosis is endoscopy with biopsy, but CT scan is a possible alternative. The primary objective of this study is to identify the diagnostic performance of CT in the evaluation of ICI enterocolitis. METHODS: With institutional review board approval, we conducted a retrospective cohort study of patients who received ICI therapy between 2015 and 2019 across a healthcare system. Patients were included if they underwent both abdominal CT and endoscopy with biopsy within 3 days. The radiological and pathological diagnoses, as well as clinical characteristics, were extracted from the electronic medical record. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT for diagnosing ICI enterocolitis when compared with tissue diagnosis. RESULTS: Of the 4474 patients screened, 138 met inclusion criteria. Most common tumor types were melanoma (37%) and lung cancer (19%). Seventy-four per cent were treated with antiprogrammed cell death (PD-1)/PD-L1 therapy. Thirty-nine per cent had signs of enterocolitis on CT scan and 58% had biopsy-proven ICI enterocolitis. Sensitivity and specificity of CT were 50% and 74%, respectively. PPV was 73% and NPV was 52%. Of those with confirmed ICI enterocolitis, 70% had grade 3 or higher symptoms, 91% received steroids and 40% received infliximab. CONCLUSION: The performance of CT scan for diagnosis of ICI enterocolitis is moderate to poor and does not replace endoscopy with biopsy.


Assuntos
Enterocolite/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Am J Case Rep ; 21: e922521, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32989210

RESUMO

BACKGROUND Nosocomial diarrhea affects 12% to 32% of hospitalized patients. Before the development of the Clostridium difficile cytotoxin assay in the 1970s, Staphylococcus aureus was frequently implicated as a cause of hospital-acquired infectious colitis, particularly in association with recent antibiotic therapy or abdominal surgery. Decreased utilization of stool culture has reduced the recognition of S. aureus as a rare, but historically important, cause of enterocolitis. CASE REPORT An 81-year-old man with no recent history of travel, exposure to potential infectious sources (e.g., sick contacts, animals, undercooked foods), or antibiotic or proton-pump inhibitor use was admitted for a Whipple procedure (expanded intraoperatively with total pancreatectomy, splenectomy, and portal vein resection) for stage III pancreatic adenocarcinoma. On postoperative day (POD) 5, the patient developed large-volume watery diarrhea that did not improve with tube feeding cessation and oral pancreatic enzyme replacement. He subsequently became clinically septic on POD10, and workup revealed severe radiographic sigmoid and rectal colitis and methicillin-resistant S. aureus (MRSA) bacteremia. Polymerase chain reaction testing for C. difficile was negative twice (POD5 and POD12). He was diagnosed with MRSA proctocolitis and improved with initiation of oral and intravenous vancomycin. CONCLUSIONS We describe a case of staphylococcal enterocolitis, a previously common cause of nosocomial diarrhea that has become increasingly underappreciated since the advent of culture-independent stool testing for C. difficile. Increased awareness of this entity, especially when Clostridium assays are negative, may guide more effective treatment of hospital-acquired infection.


Assuntos
Adenocarcinoma , Clostridioides difficile , Enterocolite , Staphylococcus aureus Resistente à Meticilina , Neoplasias Pancreáticas , Infecções Estafilocócicas , Adenocarcinoma/tratamento farmacológico , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Enterocolite/diagnóstico , Enterocolite/tratamento farmacológico , Humanos , Masculino , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
16.
Aliment Pharmacol Ther ; 52(9): 1432-1452, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920854

RESUMO

BACKGROUND: Immune checkpoint inhibitors have revolutionised cancer treatment, but at the cost of off-target immune-mediated organ damage. This includes checkpoint inhibitor-induced enterocolitis which frequently requires hospitalisation and may be life-threatening. Empiric treatment typically includes corticosteroids and infliximab, although no large-scale studies have confirmed their effectiveness. AIM: To investigate the effectiveness of anti-inflammatory therapy in checkpoint inhibitor-induced enterocolitis METHODS: We performed a systematic review and meta-analysis of studies reporting clinical outcomes of checkpoint inhibitor-induced enterocolitis in adult cancer patients treated with anti-inflammatory agents. We searched Medline, EMBASE, and the Cochrane library through April and extracted the proportion of patients responding to anti-inflammatory therapy. Variation in effect size was studied using a random-effects meta-regression analysis, with checkpoint inhibitor agent and tumour type as the variables. RESULTS: Data were pooled from 1210 treated patients across 39 studies. Corticosteroids were effective in 59% (95% CI 54- 65) of patients, with response significantly more favourable in patients treated with anti-PD-1/L1 monotherapy, compared with anti-CTLA-4 containing regimens (78%, 95% CI 69-85 vs 56 %, 95% CI 49-63, P = 0.003), and more favourable in lung cancer patients compared with melanoma patients (88%, 95% CI 62-97 vs 55%, 95% CI 47-63, P = 0.04). Infliximab was effective in 81% (95% CI 73-87) of patients, and vedolizumab in 85% (95% CI 60-96). CONCLUSION: Corticosteroids, infliximab and vedolizumab, are effective in the treatment of checkpoint inhibitor-induced enterocolitis. Checkpoint inhibitor regimen and cancer type were significant moderators in response to corticosteroid therapy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Enterocolite/induzido quimicamente , Enterocolite/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab/uso terapêutico
17.
Lancet Gastroenterol Hepatol ; 5(7): 679-697, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32553146

RESUMO

Immune checkpoint inhibitors are a novel class of cancer treatment that have improved outcomes for a subset of cancer patients. They work by antagonising inhibitory immune pathways, thereby augmenting immune-mediated antitumour responses. However, immune activation is not cancer-specific and often results in the activation of immune cells in non-cancer tissues, resulting in off-target immune-mediated injury and organ dysfunction. Diarrhoea and gastrointestinal tract inflammation are common and sometimes serious side-effects of this type of therapy. Prompt recognition of gastrointestinal toxicity and, in many cases, rapid institution of anti-inflammatory or biologic therapy (or both) is required to reverse these complications. Management of organ-specific complications benefits from multidisciplinary input, including engagement with gastroenterologists for optimal management of immune checkpoint inhibitor-induced enterocolitis. In this British Society of Gastroenterology endorsed guidance document, we have developed a consensus framework for the investigation and management of immune checkpoint inhibitor-induced enterocolitis.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Enterocolite/induzido quimicamente , Neoplasias/tratamento farmacológico , Sociedades Médicas/organização & administração , Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/toxicidade , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/toxicidade , Consenso , Endoscopia/métodos , Endoscopia do Sistema Digestório/métodos , Enterocolite/tratamento farmacológico , Enterocolite/metabolismo , Gastroenterologia/organização & administração , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/patologia , Guias como Assunto , Humanos , Infliximab/uso terapêutico , Lactoferrina/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Administração dos Cuidados ao Paciente/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Reino Unido/epidemiologia
19.
Intern Med ; 59(4): 519-525, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31645533

RESUMO

A 64-year-old Japanese man suffered cardiopulmonary arrest, which may have resulted from sepsis and/or hyperosmolar hyperglycemic non-ketonic coma, and was admitted after successful resuscitation. He had watery diarrhea on day 18 and was diagnosed with cytomegalovirus enterocolitis. In addition, computed tomography performed on day 27 and colonoscopy revealed gastric emphysema and intestinal pseudolipomatosis, respectively. This report is the first to describe a patient with cytomegalovirus enterocolitis and subsequent gastric emphysema and pseudolipomatosis. Gastrointestinal cytomegalovirus infection may underlie gastric emphysema and intestinal pseudolipomatosis, particularly in patients with relative or obvious immune dysfunction.


Assuntos
Cefmetazol/uso terapêutico , Colite/virologia , Infecções por Citomegalovirus/etiologia , Enfisema/etiologia , Enterocolite/tratamento farmacológico , Enterocolite/etiologia , Enterocolite/virologia , Ressuscitação/efeitos adversos , Antibacterianos/uso terapêutico , Povo Asiático , Colonoscopia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Enfisema/diagnóstico , Enfisema/terapia , Enterocolite/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
BMJ Case Rep ; 12(5)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142484

RESUMO

Diagnosis of postenteritic reactive arthritis (ReA) is a challenge and might have a broad range of differential diagnoses. A 50-year-old man was referred to our attention because of persistent inflammatory low back pain and asymmetric oligoarthritis. The clinical history was positive for diarrhoea in the previous 3 months. Inflammatory bowel disease, Whipple and celiac diseases were carefully excluded. In addition, serology, stool cultures, biopsies from the upper gastrointestinal tract yielded negative results for infections. A presumptive diagnosis of ReA was done and a non-steroidal anti-inflammatory drug trial prescribed. Persistence of symptoms prompted us for a second look of the colon. Biopsy collected from the terminal ileum were cultured and surprisingly colonies of Hafnia alvei, a rod-shaped Enterobacteriaceae, were detected. Treatment with ciprofloxacin leads to fast symptoms resolution. Although enterocolitis from H. alvei has been rarely reported, the culture of intestinal specimens might be recommended in the work-up of patients with suspected postenteritic ReA.


Assuntos
Artrite Reativa/microbiologia , Infecções por Enterobacteriaceae/diagnóstico por imagem , Hafnia alvei , Antibacterianos/administração & dosagem , Artrite Reativa/diagnóstico por imagem , Ciprofloxacina/administração & dosagem , Diagnóstico Diferencial , Esquema de Medicação , Quimioterapia Combinada , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterocolite/tratamento farmacológico , Enterocolite/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/administração & dosagem , Proibitinas , Cintilografia/métodos , Resultado do Tratamento
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