scholarly journals Clinicopathological and Molecular Features of Patients with Early and Late Recurrence after Curative Surgery for Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1883
Author(s):  
Yuan-Tzu Lan ◽  
Shih-Ching Chang ◽  
Pei-Ching Lin ◽  
Chun-Chi Lin ◽  
Hung-Hsin Lin ◽  
...  

Background: Few reports have investigated genetic alterations between patients with early and late recurrence following curative surgery for colorectal cancer (CRC). Methods: A total of 1227 stage I–III CRC patients who underwent curative resection were included retrospectively. Among them, 236 patients had tumor recurrence: 139 had early (<2 years after surgery) and 97 had late (≥2 years after surgery) recurrence. Clinicopathological features and genetic alterations were compared between the two groups. Results: Compared to those with late recurrence, patients with early recurrence were more likely to have advanced pathological node (N) categories; tumor, node, metastasis (TNM) stages; adjuvant chemotherapy treatment; liver metastases; APC mutations; and worse five-year overall survival rates. Patients with right-sided colon cancer were more likely to develop early recurrence than were those with left-sided colon cancer or rectal cancer. Regarding rectal cancer, patients with early recurrence were more likely to be at advanced pathological N categories and TNM stages than those with late recurrence. Multivariate analysis revealed old age, early recurrence, multiple-site recurrence, and BRAF and NRAS mutations to be independent prognostic factors. Conclusion: CRC patients with early recurrence have a worse OS rate and more APC mutations than those with late recurrence.

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan-Tzu Lan ◽  
Shih-Ching Chang ◽  
Pei-Ching Lin ◽  
Chun-Chi Lin ◽  
Hung-Hsin Lin ◽  
...  

BackgroundThe prognosis of mucinous adenocarcinoma (MAC) and non-mucinous adenocarcinoma (NMAC) in colorectal cancer (CRC) is controversial, and the molecular differences between them are unclear.MethodsBetween 2000 and 2010, a total of 1,483 CRC patients were included. Among them, 73 patients (4.9%) were diagnosed with MAC. The clinicopathological features and genetic alterations were compared between MAC and NMAC.ResultsAfter propensity score matching to balance age and sex between MAC and NMAC patients, 292 CRC patients (73 MAC and 219 NMAC) were enrolled in the analysis at a 1:3 ratio. In right-sided colon cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, and advanced T category and tumor, node, metastasis (TNM) stage, chemotherapy, and a similar 5-year overall survival (OS) rate compared with patients with NMAC. In left-sided colon cancer and rectal cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, lymphovascular invasion, advanced T and N categories and TNM stages, chemotherapy, and a worse 5-year OS rate than patients with NMAC. Regarding genetic alterations, for NMAC, right-sided colon cancer had more BRAF mutations than left-sided colon cancer and rectal cancer. For MAC, right-sided colon cancer was associated with more microsatellite instability-high tumors and more AKT1 mutations than left-sided colon cancer and rectal cancer.ConclusionThe genetic alterations are distinct between MAC and NMAC in CRC. Tumor location may have an impact on genetic alterations and patient prognosis in MAC and NMAC.


Author(s):  
Felix Wiesmueller ◽  
Rolf Schuetz ◽  
Melanie Langheinrich ◽  
Maximilian Brunner ◽  
Georg F. Weber ◽  
...  

Abstract Purpose There is no evidence-based definition of early recurrence following resection of colorectal cancer. The purpose of this study is to define a point that discriminates between early and late recurrence in patients who have undergone colorectal cancer resection with curative intent and to analyze associated risk factors. Methods A retrospective single-center cohort study was performed at a university hospital recognized as a comprehensive cancer center, specializing in colorectal cancer surgery. Patient data were retrieved from a prospectively maintained institutional database. Included patients underwent resection for primary, non-metastatic colorectal carcinomas with curative intent between 1995 and 2010. Aims of the study were (1) to define the optimal cut-off point of recurrence-free survival based on overall survival using a minimum p value approach and (2) to identify patterns of initial recurrence and putative risk factors for early recurrence using regression models. Results Recurrence was diagnosed in 412 of 1893 patients. Statistical analysis suggested that a recurrence-free survival of 16 months could be used to distinguish between early and late recurrence based on overall survival (p < 0.001). Independent risk factors for early recurrence included advanced pT categories (pT3,4/ypT3,4) and positive lymph node status (pN+/ypN+). Early recurrence was independent of site of recurrence and was associated with worse prognosis. Conclusions Recurrence of colorectal carcinoma within 16 months after primary treatment should be labeled as “early.” Tumor categories pT3,4/ypT3,4 and positive lymph node status pN+/ypN+ are predictive of early recurrence.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xi Yang ◽  
Quan Qi ◽  
Yuefen Pan ◽  
Qing Zhou ◽  
Yinhang Wu ◽  
...  

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.


2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Anette Hjartåker ◽  
Bjarte Aagnes ◽  
Trude Eid Robsahm ◽  
Hilde Langseth ◽  
Freddie Bray ◽  
...  

Objective. A shift in the total incidence from left- to right-sided colon cancer has been reported and raises the question as to whether lifestyle risk factors are responsible for the changing subsite distribution of colon cancer. The present study provides a review of the subsite-specific risk estimates for the dietary components presently regarded as convincing or probable risk factors for colorectal cancer: red meat, processed meat, fiber, garlic, milk, calcium, and alcohol.Methods. Studies were identified by searching PubMed through October 8, 2012 and by reviewing reference lists. Thirty-two prospective cohort studies are included, and the estimates are compared by sex for each risk factor.Results. For alcohol, there seems to be a stronger association with rectal cancer than with colon cancer, and for meat a somewhat stronger association with distal colon and rectal cancer, relative to proximal colon cancer. For fiber, milk, and calcium, there were only minor differences in relative risk across subsites. No statement could be given regarding garlic. Overall, many of the subsite-specific risk estimates were nonsignificant, irrespective of exposure.Conclusion. For some dietary components the associations with risk of cancer of the rectum and distal colon appear stronger than for proximal colon, but not for all.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Elena Orsenigo ◽  
Giulia Gasparini ◽  
Michele Carlucci

Many colorectal resections do not meet the minimum of 12 lymph nodes (LNs) recommended by the American Joint Committee on Cancer for accurate staging of colorectal cancer. The aim of this study was to investigate factors affecting the number of the adequate nodal yield in colorectal specimens subject to routine pathological assessment. We have retrospectively analysed the data of 2319 curatively resected colorectal cancer patients in San Raffaele Scientific Institute, Milan, between 1993 and 2017 (1259 colon cancer patients and 675 rectal cancer patients plus 385 rectal cancer patients who underwent neoadjuvant therapy). The factors influencing lymph node retrieval were subjected to uni- and multivariate analyses. Moreover, a survival analysis was carried out to verify the prognostic implications of nodal counts. The mean number of evaluated nodes was 24.08±11.4, 20.34±11.8, and 15.33±9.64 in surgically treated right-sided colon cancer, left-sided colon cancer, and rectal tumors, respectively. More than 12 lymph nodes were reported in surgical specimens in 1094 (86.9%) cases in the colon cohort and in 425 (63%) cases in the rectal cohort, and patients who underwent neoadjuvant chemoradiation were analysed separately. On univariate analysis of the colon cancer group, higher LNs counts were associated with female sex, right colon cancer, emergency surgery, pT3-T4 diseases, higher tumor size, and resected specimen length. On multivariate analysis right colon tumors, larger mean size of tumor, length of specimen, pT3-T4 disease, and female sex were found to significantly affect lymph node retrieval. Colon cancer patients with 12 or more lymph nodes removed had a significantly better long-term survival than those with 11 or fewer nodes (P=0.002, log-rank test). Rectal cancer patients with 12 or more lymph nodes removed approached but did not reach a statistically different survival (P=0.055, log-rank test). Multiple tumor and patients’ factors are associated with lymph node yield, but only the removal of at least 12 lymph nodes will reliably determine lymph node status.


Mutagenesis ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 207-219
Author(s):  
Hongyao Yu ◽  
Kari Hemminki

Abstract We review here data on familial risk in colorectal cancer (CRC) generated from the Swedish Family-Cancer Database, the largest resource of its kind in the world. Although the concordant familial risk for CRC (i.e. CRC risk in families of CRC patients) has been reasonably well established, the studies on discordant familial risks (i.e. CRC risk in families with any other cancers) are rare. Because different cancers could be caused by shared genetic susceptibility or shared environment, data of associations of discordant cancers may provide useful information for identifying common risk factors. In analyses between any of 33 discordant cancers relative risks (RRs) for discordant cancers were estimated in families with increasing numbers of probands with CRC; in the reverse analyses, RRs for CRC were estimated in families with increasing numbers of probands with discordant cancers. In separate analyses, hereditary non-polyposis colorectal cancer (HNPCC) families were excluded from the study, based on HNPCC related double primary cancers, to assess the residual familial RRs. We further reviewed familial risks of colon and rectal cancers separately in search for distinct discordant associations. The reviewed data suggested that colon cancer was associated with a higher familial risk for CRC compared to rectal cancer. The previous data had reported associations of CRC with melanoma, thyroid and eye cancers. Nervous system cancer was only associated with colon cancer, and lung cancer only associated with rectal cancer. The reviewed data on discordant association may provide guidance to gene identification and may help genetic counseling.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14114-e14114
Author(s):  
Justin Y Jeon ◽  
Deok Hyun Jeong ◽  
Min Keun Park ◽  
Jennifer A. Ligibel ◽  
Jeffrey A. Meyerhardt ◽  
...  

e14114 Background: Background: Conflicting results have been reported whether pre diagnosis diabetes mellitus (DM) influence survival of colorectal cancer patients or not. Therefore, we determine the influence of DM on long-term outcomes of stage 1-3 patients with resected colon and rectal cancer. Methods: This prospective study include a total of 4,131 participants who were treated for cancer between 1995 and 2005 in South Korea in a single hospital (Non DM: 3,614 patients, DM: 517 patients) with average follow up period of 12 years. We analyzed differences in all cause mortality, disease free survival (DFS), recurrence free survival (RFS) and colorectal cancer-specific mortality between colorectal patients with DM and those without DM. Results: After adjustment for potential confounders, pre-diagnosis DM significantly associated with increased all cause mortality (HR: 1.46, 95% CI: 1.11-1.92), and recurrence free survival reduced DFS (HR: 1.45, 95%CI: 1.15-1.84) and RFS (HR: 1.32, 95% CI: 0.98-1.76) in colon cancer patients but not in rectal cancer patients. In colon cancer patients, DM negatively affects the survival outcome of proximal colon cancer (HR: 2.08, 95%CI: 1.38-3.13), but not of distal cancer (HR:1.34, 95% CI: 0.92-1.96). Conclusions: To our knowledge, the current study first reported the effects of pre-diagnosis DM on survival outcome of colorectal cancer are site specific (proximal colon, distal colon and rectum). The current study was supported by the National Research Foundation of Korea (KRF) (No. 2011-0004892) and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1120230). [Table: see text]


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