RESUMEN
BACKGROUND: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. PATIENTS AND METHODS: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. RESULTS: Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01). CONCLUSION: ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.
Asunto(s)
Insuficiencia Pancreática Exocrina , Hiperglucemia , Pancreatitis , Esteatorrea , Humanos , Pancrelipasa/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Esteatorrea/inducido químicamente , Esteatorrea/complicaciones , Esteatorrea/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Casos y Controles , Enfermedad Aguda , Pancreatitis/inducido químicamente , Pancreatitis/complicaciones , Pancreatitis/tratamiento farmacológico , Insuficiencia Pancreática Exocrina/inducido químicamente , Insuficiencia Pancreática Exocrina/epidemiología , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Hiperglucemia/inducido químicamente , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Pérdida de PesoAsunto(s)
Diarrea/inducido químicamente , Diarrea/fisiopatología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Colitis/inducido químicamente , Colitis/fisiopatología , Colon/fisiopatología , Colonoscopía , Enterocolitis Seudomembranosa/inducido químicamente , Enterocolitis Seudomembranosa/diagnóstico , Enterocolitis Seudomembranosa/fisiopatología , Motilidad Gastrointestinal/fisiología , Humanos , Irinotecán , Contracción Muscular/fisiología , ATPasa Intercambiadora de Sodio-Potasio/efectos de los fármacos , Esteatorrea/inducido químicamenteRESUMEN
BACKGROUND: Evidence for beneficial effects of squalene on ultraviolet (UV)-induced photoageing of the skin is lacking. AIM: To investigate whether squalene supplementation improves signs and molecular markers of photoageing in human skin in vivo. METHODS: In total, 40 female volunteers aged > 50 years received two different doses [13.5 g/day (low-dose group) and 27 g/day (high-dose group)] of squalene for 90 days. At baseline and at the completion of the study, facial wrinkles were measured using skin replicas. Skin samples were taken to compare type I procollagen and matrix metalloproteinase 1 mRNA levels by real-time reverse-transcriptase PCR, and for type I procollagen immunostaining. Skin samples were also taken 24 h after 2 x minimal erythema dose (MED) of UV irradiation before and after squalene intake to assess UV-induced thymine dimer formation and keratinocytic apoptosis. RESULTS: In total, 37 subjects completed the trial. Transient loose stool was experienced by 35% of volunteers in the low-dose group and 55% in the high-dose group. Facial wrinkles decreased significantly (P < 0.05) in the high-dose group, while procollagen type I mRNA levels and MED increased significantly in the low-dose group. Procollagen immunostaining tended to increase in both groups. Facial erythema decreased and pigmentation increased significantly in both groups. UV-induced keratinocytic apoptosis and thymine dimer staining were substantially reduced in both groups. CONCLUSIONS: Daily ingestion of 13.5 or 27 g of squalene per day resulted in antiageing effects in photoaged skin. However, in view of the frequent incidence of loose stool experienced by the subjects, the risk-benefit ratio of high-dose squalene supplementation is too high to recommend it for treating skin ageing.
Asunto(s)
Colágeno Tipo I/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Escualeno/administración & dosificación , Anciano , Daño del ADN/efectos de los fármacos , Diarrea/inducido químicamente , Suplementos Dietéticos/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Pigmentación de la Piel/efectos de los fármacos , Escualeno/efectos adversos , Esteatorrea/inducido químicamente , Resultado del Tratamiento , Rayos Ultravioleta/efectos adversosAsunto(s)
Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Hígado/fisiopatología , Trastornos Psicóticos/tratamiento farmacológico , Esteatorrea , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Femenino , Humanos , Hígado/metabolismo , Persona de Mediana Edad , Esteatorrea/inducido químicamente , Esteatorrea/metabolismo , Esteatorrea/fisiopatologíaRESUMEN
Neomycin administered to rats subjected to lymphatic fistula and treated with 14C-labelled oleic acid did not decrease either the absorption or the esterification of this organic acid. The results appear to indicate that neomycin has no effect on the intestinal mucosa.
Asunto(s)
Antibacterianos/farmacología , Absorción Intestinal/efectos de los fármacos , Síndromes de Malabsorción/inducido químicamente , Neomicina/farmacología , Ácido Oléico/farmacocinética , Administración Oral , Anastomosis Quirúrgica , Animales , Cateterismo , Esterificación/efectos de los fármacos , Linfa/metabolismo , Síndromes de Malabsorción/fisiopatología , Neomicina/toxicidad , Sistema Porta/metabolismo , Ratas , Esteatorrea/inducido químicamente , Estómago , Conducto Torácico/cirugíaRESUMEN
Intragastrically administered 14C-triolein was observed in fistula-derived lymph from rats treated with neomycin and controls. Absorption was much reduced in the treated animals, indicating (contrary to the literature data) that neomycin malabsorption also occurs in this species. The slight amount absorbed followed normal routes. It is suggested that the antibiotic acts on the intestinal content and not on the mucosa.