Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion.

BACKGROUND AND AIMS: The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI. METHODS: From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0. RESULTS: Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed. CONCLUSIONS: Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Evaluation of fecal protein S100A12 in patients with inflammatory bowel disease / Avaliação da proteína fecal s100q12 em pacientes com doença inflamatória intestinal

BACKGROUND AND OBJECTIVE: The diagnosis and evaluation of inflammatory bowel disease is quite complex. An ideal, noninvasive marker for this disease is quite urgently needed. Fecal S100A12 is a member of the S100 protein family and is secreted by activated neutrophils. We aim to evaluate it as a biomarker for inflammatory bowel disease patients in China. METHODS: Fecal S100A12 was measured in 18 Crohn's disease, 21 ulcerative colitis, and 17 healthy controls. Diagnostic value was evaluated by receiver operating characteristic (ROC) analysis in comparison with C-reactive protein and erythrocyte sedimentation rate. The correlation between fecal S100A12 and clinical characteristics was also evaluated. RESULTS: We found significant increases (p<0.01) in the diagnostic value of S100A12 in both Ulcerative Colitis and Crohn's Disease when compared to healthy controls. In ulcerative colitis, fecal S100A12 correlated with fecal occult blood (p=0.02, r=0.55); in Crohn's disease, it correlated with disease duration, albumin and platelet levels (p=0.01, r=-0.53; p<0.01, r=-0.65; p=0.04, r=0.45. respectively). No correlation occurred between fecal S100A12 and other clinical conditions. CONCLUSION: Fecal S100A12 is valuable in distinguishing inflammatory bowel disease patients versus healthy controls. However, the sensitivity and specificity are limited when compared with that described in western countries. The correlation between S100A12 and clinical characteristics is limited as well. More research is need to better explore this interaction in Chinese patients.

JUSTIFICATIVA E OBJETIVO: O diagnóstico e avaliação da doença inflamatória intestinal é bastante complexo. Um marcador ideal, não invasivo para esta doença é urgentemente necessário. O S100A12 fecal é um membro da família de proteínas S100 e é secretado por neutrófilos ativados. Pretendemos avaliá-lo como biomarcador para pacientes com doença inflamatória intestinal na China. MÉTODOS: a proteína fecal S100A12 foi medida em 18 pacientes com Moléstia de Crohn, 21 pacientes com Colite Ulcerativa e 17 voluntários saudáveis (controles). O valor diagnóstico foi avaliado através da análise da característica de operação do receptor (ROC) em comparação com a proteína C reativa e com a taxa sedimentação eritrocitária. A correlação entre S100A12 fecal e características clínicas também foi avaliada. RESULTADOS: Observamos aumentos significativos (p < 0.01) no valor diagnóstico de S100A12 tanto na Colite Ulcerativa quanto na Doença de Crohn quando comparados aos controles saudáveis. Na colite ulcerativa, a proteína S100A12 fecal correlacionou com sangue oculto fecal (p = 0,02, r = 0,55); Na doença de Crohn, correlacionou com a duração da doença, albumina e níveis de plaquetas (p = 0,01, r = -0,53; p <0,01, r = -0,65; p = 0,04, r = 0,45, respectivamente). Não houve correlação entre S100A12 fecal e outras condições clínicas. CONCLUSÃO: O S100A12 fecal é valioso para distinguir pacientes com doença inflamatória intestinal versus controles saudáveis. No entanto, a sensibilidade e especificidade é limitada quando comparada com a descrita nos países ocidentais. A correlação entre S100A12 e características clínicas é limitada. Mais pesquisas são necessárias para explorar melhor essa interação em pacientes chineses.