RESUMO
BACKGROUND: Chronic pouchitis and Crohn's disease after Ileal pouch anal anastomosis (IPAA) for ulcerative colitis could be a larger issue than previously reported. METHODS: All patients receiving care for their IPAA over a 10-year period at a community hospital were included. Primary outcomes were incidence of Crohn's disease and pouchitis. RESULTS: The study included 380 IPAA patients. Indication for pouch creation was either UC (n = 362) or indeterminate colitis (n = 18). Cumulative incidence of Crohn's was 19.5%. Five-, 10- and 20-year incidence of Crohn's was 3.4%, 8.4% and 16.9%. Chronic pouchitis occurred in 28.7%. Mean time to pouchitis and Crohn's diagnosis was 8.4 (SD ± 8.0) and 11.6 (SD ± 7.5) years. Pouch failure occurred in 12.4%. Patients who developed Crohn's were more likely to suffer pouchitis and pouch failure (OR 3.5, 95%CI 2.0-6.0 and 5.3, 95%CI 2.8-10.1). CONCLUSION: During long term follow up, almost 20% are diagnosed with Crohn's contributing significantly to pouch failure.
Assuntos
Colite Ulcerativa , Colite , Bolsas Cólicas , Doença de Crohn , Pouchite , Proctocolectomia Restauradora , Colite/cirurgia , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Doença de Crohn/cirurgia , Humanos , Pouchite/epidemiologia , Pouchite/etiologia , Proctocolectomia Restauradora/efeitos adversosRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma has a high rate of recurrence after resection. We aimed to investigate patterns of recurrence of pancreatic ductal adenocarcinoma to identify opportunities for targeted intervention toward improving survival. METHODS: This was a retrospective analysis of consecutive patients that underwent curative-intent resection for pancreatic ductal adenocarcinoma between 2007 and 2015. Recurrence and survival were analyzed based on site of recurrence. Multiple clinicopathologic factors were calculated for likelihood of site-specific recurrence. RESULTS: The study included 221 patients with median follow-up of 83 months. Median overall and recurrence-free survival was 19 and 13 months, respectively. Recurrence was observed in 71.9% patients. Local recurrence occurred in 16.4%, distant recurrence in 67.3%, and combined in 15.9%. The most common site of distant recurrence was the liver (49.7%) followed by lung (31.8%) and peritoneum (16.6%). Median time to liver recurrence was shortest (5 months, 95% confidence interval 1.7-8.3) and post recurrence survival was poor (4 months, 95% confidence interval 1.9-6.1). Patients with poorly differentiated tumors on pathology were 4.8 times more likely to recur in the liver (odds ratio 4.83, 95% confidence interval 1.7-13.9). CONCLUSION: Liver metastasis after resection of pancreatic ductal adenocarcinoma occurs most frequently, earliest after surgery, and is rapidly fatal. Liver-directed therapies represent a target for future study.
Assuntos
Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Idoso , Carcinoma Ductal Pancreático/cirurgia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pancreatectomia , Pancreaticoduodenectomia , Prognóstico , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
FCRL5+ atypical memory B cells (atMBCs) expand in many chronic human infections, including recurrent malaria, but studies have drawn opposing conclusions about their function. Here, in mice infected with Plasmodium chabaudi, we demonstrate expansion of an antigen-specific FCRL5+ population that is distinct from previously described FCRL5+ innate-like murine subsets. Comparative analyses reveal overlapping phenotypic and transcriptomic signatures between FCRL5+ B cells from Plasmodium-infected mice and atMBCs from Plasmodium-exposed humans. In infected mice, FCRL5 is expressed on the majority of antigen-specific germinal-center-derived memory B cells (MBCs). Upon challenge, FCRL5+ MBCs rapidly give rise to antibody-producing cells expressing additional atypical markers, demonstrating functionality in vivo. Moreover, atypical markers are expressed on antigen-specific MBCs generated by immunization in both mice and humans, indicating that the atypical phenotype is not restricted to chronic settings. This study resolves conflicting interpretations of atMBC function and suggests FCRL5+ B cells as an attractive target for vaccine strategies.
Assuntos
Linfócitos B/imunologia , Memória Imunológica , Malária/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Células Cultivadas , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Plasmodium chabaudi/imunologia , Plasmodium yoelii/imunologia , Receptores Fc/genética , Receptores Fc/metabolismo , TranscriptomaRESUMO
In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection.