1、Field Cancerization In Rectal Cancer 2、Impact Of Interval Between NeoadjuvantChemoradiotherapy And Surgery For Rectal Cancer OnSurgical And Oncologic Outcome

Part I Field cancerization in rectal cancer[Background and Purpose] The development of colorectal cancer is a biology process with multiple stages and steps. There is an increasing body of evidence suggesting that the road to cancer development can begin long before the development of tumor, or indeed before any of the usual histopathological hallmarks of neoplasia. Field cancerization is used to describe pre-malignant tissue in which new cancers are more likely to arise. The concept of field cancerization has been proved in many different kinds of cancers. In this study, we collected the tissues of rectal adenocarcinoma and areas adjacent to the tumors ranging from lcm to proximal margin. Gene expression analysis was used to compare the gene expression between tumor and adjacent mucosa.[Materials and Methods] A total of 32 tumors and adjacent tissues were included in this study. All the tumors had a matching sample from 1 cm,5 cm distal to the tumor and sample from proximal margin. RNAs of these samples were isolated and mRNA microarray was analyzed with Agilent SurePrint G3 Human GE v28x60K Microarray.Multiple bioinformatics softwares and methods were used to analyze the data.[Results] The pattern of gene expression was significantly different from tumor and adjacent tissues. The Principle Components Analysis (PCA) showed that gene expression of adjacent mucosa was more different from tumor as the distance form tumor increased. The genes up-regulated in tumor were involved in mitosis, RNA processing, translation, and cell cycle, etc. The genes down-regulated in tumor were associated with apoptosis, programmed cell death, cell junction, etc. Gene Set Enrichment Analysis showed that the pathways involved in tumor development and progress were significantly enriched in tumor and adjacent 1cm mucosa, when compared to adjacent 5cm mucosa. Similarly, the pathways involved in tumor inhibition were significantly enriched in adjacent mucosae, when compared to tumor tissues. Finally, we found that a total of 382 genes were consistently differentially expressed among tumor, adjacent lcm and 5cm tissue. According to these differentially expressed 382 genes, colorectal cancer patients in GES1433 and GSE17536 could be divided into two groups with good prognosis and worse prognosis, respectively.[Conclusions] Field cancerization was confirmed by gene expression profiles. The adjacent mucosa more close to tumor, the pattern of gene expression is more similar to that of tumor. Furthermore, the differentially expressed genes were siginificantly associated with tumor prognosis, which indicated that these genes may paly an important role in tumor development and progress.Part II Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome[Background and Purpose] Neoadjuvant chemoradiotherapy(CRT) followed by total mesorectal excision(TME) has become the standard of care for patients with locally advanced rectal cancer. Tumor regression and radiation-induced necrosis are a time-dependent phenomenon. However, the optimal interval between long-course neoadjuvant chemoradiotherapy and surgery is controversial. The aim of this study was to evaluate the effect of a longer interval between neoadjuvant therapy and surgery on pathologic response and on surgical and oncologic outcome.[Materials and Methods] A total of 233 consecutive patients with clinical stage Ⅱ and III rectal cancer were included. Data on the neoadjuvant regimen, neoadjuvant-surgery interval, type of surgery, operative time, estimated blood loss, perioperative complications, postoperative return of gastrointestinal function, length of hospital stay, final pathology, disease recurrence, and mortality were prospectively collected and analyzed.[Results] The median interval between the completion of neoadjuvant therapy and surgery was 50 days(range 25-105 days).Patients were divided into two groups according to the neoadjuvant-surgery interval:short-interval group (≤7 weeks, n= 111), and long-interval group (>7 weeks, n= 122). The two groups were comparable in terms of demographics, tumor, and treatment characteristics. Operative time, perioperative complications, and return of gastrointestinal function were not influenced by a longer interval. Patients in the long-interval group had a significantly higher pathologic complete response (pCR) rate (27.1% vs.15.3%, P=0.029), and a decreased rate of circumferential resection margin involvement (1.6% vs.8.1%, P=0.020). After a median follow-up of 42 months (range 6-90 months), the 3-year local recurrence rate was 12.9% in the short-interval group versus 4.8% in the long-interval group (p= 0.025).[Conclusions] A neoadjuvant-surgery interval>7 weeks is safe and is associated with a higher rate of pCR and RO resection, and decreased local recurrence.