RESUMO
Aristolochic acid (AA) is a bioactive component of Chinese herbs, dietary supplements, slimming pills and contaminated flour, which is known to induce chronic tubulointerstitial disease. AA is also shown to be involved in the genesis of the upper urinary tract urothelial carcinoma (UTUC) and some other cancers, but its tumorigenic role is far to be understood. We performed a systematic literature review regarding the involvement of AA in malignant processes and molecular pathways of carcinogenesis. Twenty representative papers were selected for this review. These papers reveal that AA exposure increases the risk for UTUC, renal cell carcinoma, hepatocellular carcinoma, gastric and small intestine cancer. The role of AA in lymphomagenesis is also proposed. The A:T to T:A transversions occurring in the 5'-CpApG-3' trinucleotide context of the TP53 gene is considered to be the signature mutation of AA. Genes including H-ras, FGFR3, N-ras and BRCA2 are also involved. For further understanding of AA's role in tumorigenesis, the exploration of the AA's molecular signature is necessary.
Assuntos
Ácidos Aristolóquicos/efeitos adversos , Neoplasias/induzido quimicamente , Carcinogênese , Humanos , Neoplasias/patologiaRESUMO
A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.