A distal margin of 1 mm is associated with worse oncologic results. Our data indicate the importance of achieving a clear distal margin in the surgical treatment of rectal cancer. Adjuvant therapy should be used in these patients to reduce recurrence. See Video Abstract at http://links.lww.com/DCR/A408.
IntroductionPreoperative chemoradiotherapy (CRT), followed by total mesorectal excision, has become the standard of care for patients with clinical stages II and III rectal cancer. Patients with pathologic complete response (pCR) to preoperative CRT have been reported to have better outcomes than those without pCR. However, the factors that predict the response to neoadjuvant CRT have not been well defined. In this study, we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer.MethodsA total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT, followed by curative surgery, between 2005 and 2013 were included. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR and non-pCR groups. The clinical parameters were analyzed by univariate and multivariate analyses, with pCR as the dependent variable.ResultsOf the 323 patients, 75 (23.2%) achieved pCR. The two groups were comparable in terms of age, sex, body mass index, tumor stage, tumor location, tumor differentiation, radiation dose, and chemotherapy regimen. On multivariate analysis, a pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL [odds ratio (OR) = 2.170, 95% confidence interval (CI) = 1.195–3.939, P = 0.011] and an interval of >7 weeks between the completion of chemoradiation and surgical resection (OR = 2.588, 95% CI = 1.484–4.512, P = 0.001) were significantly associated with an increased rate of pCR.ConclusionsThe pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR. These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies.
Desmoid tumors are rare soft tissue tumors with limited data on their management and prognosis. We sought to determine the rates of recurrence after surgery for desmoid tumors and analyze factors predictive of recurrence-free survival (RFS). From February 1976 to October 2011, 233 consecutive patients with desmoid tumors who underwent macroscopically complete resection were included in this study. Clinicopathologic and treatment characteristics were evaluated to determine predictors of recurrence. Patterns of presentation included primary (n = 156, 67.0 %) and locally recurrent (n = 77, 33.0 %) disease initially treated elsewhere. Most patients had a R0 resection (n = 169, 72.5 %). In addition to surgery, 43 (18.5 %) patients received radiotherapy and 10 (4.3 %) patients received systemic therapy. Median follow-up was 54 months; recurrence disease was observed in 62 (26.6 %) patients. The estimated 5- and 10-year RFS was 74.2 % (95 % confidence interval (CI), 68.3-80.1) and 70.7 % (95 % CI, 64.2-77.2), respectively. Factors associated with worse RFS were tumor size larger than 5 cm (hazard ratio (HR) = 3.757; 95 % CI, 1.945-7.259; p < 0.001), extra-abdominal tumor location (abdominal wall referent; HR = 3.373; 95 % CI, 1.425-7.984; p = 0.006), and R1 resection status (HR = 1.901; 95 % CI, 1.140-3.171; p = 0.014). Patients were grouped according to the number of unfavorable prognostic factors; the 10-year RFS rates of patients with zero, one, two, and three prognostic factors were 100, 86.9, 48.5, and 34.4 %, respectively (p < 0.001). Regardless of primary or recurrent disease, surgical resection remains central to the management of patients with desmoid tumors. However, there are clearly different prognostic subgroups that could benefit from different therapeutic strategies, and a wait-and-see policy is a possible option for a subset of patients.
Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients. Significantly differentially expressed genes related to the distance from the tumor were screened by linear mixed effects analysis using the lme4 package in R. The distance-related differentially expressed genes that were gradually up-regulated (n=302) or gradually down-regulated (n=568) from normal tissues to the tumor were used to construct protein-protein interaction (PPI) networks. Three subnetworks among the gradually up-regulated genes and four subnetworks among the gradually down-regulated genes were identified using the MCODE plugin in the Cytoscape software program. The most significantly enriched Gene Ontology (GO) biological process terms were “ribosome biogenesis”, “mRNA splicing via spliceosome”, and “positive regulation of leukocyte migration” for the gradually up-regulated subnetworks and “cellular calcium ion homeostasis”, “cell separation after cytokinesis”, “cell junction assembly”, and “fatty acid metabolic process” for the gradually down-regulated subnetworks. Combined with the previously constructed multistep carcinogenesis model used for the analysis, 50.59% of the genes in the subnetworks (43/85) displayed identical changes in expression from normal colon tissues to adenoma and colon cancer. We focused on the 7 genes associated with fatty acid metabolic processes in the distance-related down-regulated subnetwork. Survival analysis of patients in the CRC dataset from The Cancer Genome Atlas (TCGA) revealed that higher expression of these 7 genes, especially CPT2, ACAA2 and ACADM, was associated with better prognosis (p = 0.034, p = 0.00058, p = 0.039, p = 0.04). Cox proportional hazards regression analysis revealed that CPT2 was an independent prognostic factor (p = 0.004131). Our results demonstrate that field cancerization occurs in CRC and affects gene expression in normal tissues extending from the tumor, which may provide new insights into CRC oncogenesis and patient progression.
Background: The lymph node ratio (LNR) has been shown to be an important prognostic factor for colorectal cancer. However, studies focusing on the prognostic impact of LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) followed by curative resection have been limited. The aim of this study was to investigate LNR in rectal cancer patients who received neoadjuvant chemoradiotherapy harvested LNs, and as well as in those ≥12 harvested LNs (p<0.05). In addition, LNR had a prognostic impact on both OS and DFS in patients with N1 staging (p<0.001). Conclusions: LNR is an independent prognostic factor in ypN-positive rectal cancer patients, both in patients with <12 harvested LNs, and as well as in those ≥12 harvested LNs. LNR provides better prognostic value than pN staging. Therefore, it should be used as an additional prognostic indicator in ypN-positive rectal cancer patients.
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