ABSTRACT
DNA repair pathways are essential for maintaining genome stability, and understanding the regulation of these mechanisms may help in the design of new strategies for treatments, the prevention of platinum-based chemoresistance, and the prolongation of overall patient survival not only with respect to ovarian cancer. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) together with cytoreductive surgery (CRS) and adjuvant systemic chemotherapy is receiving more interest in ovarian cancer (OC) treatment because of the typical peritoneal spread of the disease. The aim of our study was to compare the expression level of 84 genes involved in the DNA repair pathway in tumors and the paired peritoneal metastasis tissue of patients treated with CRS/platinum-based HIPEC with respect to overall patient survival, presence of peritoneal carcinomatosis, treatment response, and alterations in the BRCA1 and BRCA2 genes. Tumors and metastatic tissue from 28 ovarian cancer patients collected during cytoreductive surgery before HIPEC with cisplatin were used for RNA isolation and subsequent cDNA synthesis. Quantitative real-time PCR followed. The most interesting findings of our study are undoubtedly the gene interactions among the genes CCNH, XPA, SLK, RAD51C, XPA, NEIL1, and ATR for primary tumor tissue and ATM, ATR, BRCA2, CDK7, MSH2, MUTYH, POLB, and XRCC4 for metastases. Another interesting finding is the correlation between gene expression and overall survival (OS), where a low expression correlates with a worse OS.
Subject(s)
DNA Glycosylases , Hyperthermia, Induced , Ovarian Neoplasms , Humans , Female , Hyperthermic Intraperitoneal Chemotherapy , Disease-Free Survival , Hyperthermia, Induced/methods , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , DNA Repair/genetics , Combined Modality Therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate , Retrospective Studies , DNA Glycosylases/geneticsABSTRACT
BACKGROUND: Endosonography-guided fine needle aspiration biopsy (EUS-FNA)-associated metachronous gastric seeding metastases (GSM) of pancreatic ductal adenocarcinoma (PDAC) represent a serious condition with insufficient evidence. METHODS: Retrospective analysis of PDAC resections with a curative-intent, proven pathological diagnosis of PDAC, preoperative EUS-FNA and post-resection follow-up of at least 60 months. The systematic literature search of published data was used for the GSM growth evaluation using Pearson correlation and the linear regression analyses. RESULTS: The inclusion criteria met 59/134 cases, 16 (27%) had retained needle tract (15 following distal pancreatectomy, 1 following pylorus-sparing head resection). In total, 3/16 cases (19%) developed identical solitary GSM (10-26th month following primary surgery) and were radically resected. A total of 30 published cases of PDAC GSM following EUS-FNA were identified. Lesion was resected in 20 distal pancreatectomy cases with complete information in 14 cases. A correlation between the metastasis size and time (r = 0.612) was proven. The regression coefficient b = 0.72 expresses the growth of 0.72 mm per month. CONCLUSIONS: The GSM represent a preventable and curable condition. A remarkably high number of GSM following EUS-FNA was identified, leading to follow-up recommendation of EUS-FNA sampled patients. Multimodal management (gastric resection, adjuvant chemotherapy) may prolong survival.
