A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

scholarly journals Systemic therapy for colorectal cancer

2003 ◽  
Vol 11 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Borut Stabuc
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Metastatic Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Phase Iii ◽  
Oral Fluoropyrimidines ◽  
Significant Difference

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

scholarly journals Subsite-Specific Dietary Risk Factors for Colorectal Cancer: A Review of Cohort Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Anette Hjartåker ◽  
Bjarte Aagnes ◽  
Trude Eid Robsahm ◽  
Hilde Langseth ◽  
Freddie Bray ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cohort Studies ◽  
Distal Colon ◽  
Proximal Colon ◽  
Risk Estimates ◽  
Specific Risk ◽  
Dietary Components

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.

Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Control Group ◽  
Significant Difference ◽  
Resected Stage

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.

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
A. M. Glas ◽  
P. Roepman ◽  
R. Salazar ◽  
G. Capella ◽  
V. Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Gene Signature ◽  
Low Risk ◽  
Stage Ii ◽  
Significant Difference ◽  
Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

Impact of diabetes on site-specific oncologic outcome in stage I-III colorectal cancer.

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Proximal Colon ◽  
Survival Outcome ◽  
Recurrence Free Survival ◽  
Site Specific ◽  
Free Survival ◽  
All Cause Mortality

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]

Clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 867-867
Author(s):  
Shusuke Yagi ◽  
Eiji Shinozaki ◽  
Keisho Chin ◽  
Mitsukuni Suenaga ◽  
Daisuke Takahari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Dose Intensity ◽  
Clinical Impact ◽  
Stage Ii ◽  
Stage Iii ◽  
Diverting Ileostomy ◽  
Grade 3

867 Background: CAPOX as adjuvant chemotherapy is a standard care option for stage III and high risk stage II colorectal cancer(CRC). And then chemotherapy induced diarrhea (CID) is known as one of the dose-limiting toxicities for CAPOX. Although diverting ileostomy is useful for preventing serious complications of high risk anastomosis, it is well recognized that high ileostomy output is hard to manage. Furthermore, the effect of diverting ileostomy on CID of adjuvant chemotherapy is unclear. In this study, we addressed the clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for CRC. Methods: Patients who diagnosed with stage III colon cancer and stage II or III rectal cancer after curative surgery and received CAPOX as adjuvant chemotherapy during 2011- 2014 were reviewed retrospectively. We investigated the relationship between diverting ileostomy and dose intensity, toxicities and disease-free survival (DFS). Results: 112 patients (median age 60 years, 52% male, 69% colon cancer, 63% stage III, median follow-up 47 months) were enrolled in this study. Of 112 patients, 100 patients were received chemotherapy without ileostomy (non-ileostomy group: NIG) and 12 patients were received chemotherapy with ileostomy (ileostomy group: IG). 112 Patients received 870 chemotherapy cycles. All treatment related grade 3/4 adverse events were documented in 39% of patients in NIG and 33% of patients in IG (P = 0.77). Grade 3/4 of CID occurred in 8% of patients in NIG and 8% of patients in IG (P = 1). Grade 3/4 of neutropenia were recognized in 21% of patients in NIG and 17% of patients in IG (P = 1). Average relative dose intensity (RDI) in NIG were 75.7% and 85.8% for capecitabine and oxaliplatin, respectively. Average RDI of capecitabine and oxaliplatin in IG were 76.1% and 82.7%, respectively. Significant difference of RDI of capecitabine and oxaliplatin were not shown in comparison between NIG and IG (P = 0.93, P = 0.63). The 3-year DFS rate was 85.0% in NIG and 75.0% in IG. The HR for DFS for NIG compared to IG was 1.709 (95% CI, 0.49 to 5.95; P = 0.40). Conclusions: The presence of diverting ileostomy does not affect RDI of CAPOX as adjuvant chemotherapy.

scholarly journals Healthy lifestyle, endoscopic screening, and colorectal cancer incidence and mortality in the United States: A nationwide cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (2) ◽  
pp. e1003522
Author(s):  
Kai Wang ◽  
Wenjie Ma ◽  
Kana Wu ◽  
Shuji Ogino ◽  
Andrew T. Chan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Health Professionals ◽  
Healthy Lifestyle ◽  
The United States ◽  
Proximal Colon ◽  
Health Study ◽  
Endoscopic Screening ◽  
Incidence And Mortality

Background Healthy lifestyle and screening represent 2 major approaches to colorectal cancer (CRC) prevention. It remains unknown whether the CRC-preventive benefit of healthy lifestyle differs by endoscopic screening status, and how the combination of healthy lifestyle with endoscopic screening can improve CRC prevention. Methods and findings We assessed lifestyle and endoscopic screening biennially among 75,873 women (Nurses’ Health Study, 1988 to 2014) and 42,875 men (Health Professionals Follow-up Study, 1988 to 2014). We defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet. We calculated hazard ratios (HRs) and population-attributable risks (PARs) for CRC incidence and mortality in relation to healthy lifestyle score according to endoscopic screening. Participants’ mean age (standard deviation) at baseline was 54 (8) years. During a median of 26 years (2,827,088 person-years) follow-up, we documented 2,836 incident CRC cases and 1,013 CRC deaths. We found a similar association between healthy lifestyle score and lower CRC incidence among individuals with and without endoscopic screening, with the multivariable HR per one-unit increment of 0.85 (95% CI, 0.80 to 0.90) and 0.85 (95% CI, 0.81 to 0.88), respectively (P-interaction = 0.99). The fraction of CRC cases that might be prevented (PAR) by endoscopic screening alone was 32% (95% CI, 31% to 33%) and increased to 61% (95% CI, 42% to 75%) when combined with healthy lifestyle (score = 5). The corresponding PAR (95% CI) increased from 15% (13% to 16%) to 51% (17% to 74%) for proximal colon cancer and from 47% (45% to 50%) to 75% (61% to 84%) for distal CRC. Results were similar for CRC mortality. A limitation of our study is that our study participants are all health professionals and predominantly whites, which may not be representative of the general population. Conclusions Our study suggests that healthy lifestyle is associated with lower CRC incidence and mortality independent of endoscopic screening. An integration of healthy lifestyle with endoscopic screening may substantially enhance prevention for CRC, particularly for proximal colon cancer, compared to endoscopic screening alone.

scholarly journals Comparison of Treatment Outcomes between Right- and Left-sided Colorectal Adenocarcinoma after Adjuvant Chemotherapy

2021 ◽  
Vol 6 (4) ◽  
pp. 389-395
Author(s):  
Dean Marvin Potato Pizarro ◽  
Carlos Dy ◽  
Mel Valerie` Cruz- Ordinario ◽  
Cyrielle Marie Atutubo
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Colorectal Adenocarcinoma ◽  
Locally Advanced ◽  
Survival Outcomes ◽  
Metastatic Setting ◽  
Significant Difference ◽  
Disease Free ◽  
Tumor Laterality

Objective: The survival outcomes of patients with metastatic colorectal adenocarcinoma based on tumor laterality has already been established based on large-scale retrospective studies. As for the non-metastatic disease, the data is much more conflicting. Local data in this population is also scarce. In this study, we determined the difference in survival of right-sided versus left-sided colorectal cancer patients after surgery and adjuvant chemotherapy. Patients and Methods: This retrospective study analyzed a total of 124 patients who were diagnosed with early to locally advanced (stage I to IVA) colorectal adenocarcinoma and underwent definitive surgery and adjuvant systemic treatment per physician’s preference. The patients were stratified according to the primary tumor laterality: Right-Sided Colon cancer (RCC) and Left-sided Colon cancer (LCC). The primary outcome being investigated is the disease-free survival (DFS) at 3 years and 5 years. Secondary outcomes are overall survival (OS) at 3 years and 5 years, and site of disease recurrence across laterality.Results: The findings did not show a significant difference in the 3-year and 5-year DFS between RCC and LCC after surgery and adjuvant chemotherapy (3-year DFS: 50.0% in the RCC group and 54.3% in the LCC group; P=.671; 5-year DFS: 36.7% in the RCC group and 36.2% in the LCC group, P=.474). The OS difference was also not significant at 3 years and 5 years (3-year OS: 68.8% in the RCC group and 73.9% in the LCC group, P=.572; 5-year OS: 31.3% in the RCC group and 26.1% in the LCC group, P=.474). The overall recurrence rate was not significantly different in both groups (65.6% in the RCC group and 66.3% in the LCC group; P=.944). Majority of the recurrences were at a distant site in both groups (61.1% in the RCC group and 69.6% in the LCC group; P=.501) and the most common were in the lungs, and liver. Conclusion: The survival outcome of non-metastatic colorectal adenocarcinoma was not significantly different between RCC and LCC after surgery and adjuvant chemotherapy. The outcome was also similar after stratification of the population into early and locally advanced disease. More diverse clinical characteristics other than tumor location may be prognostic of disease-free and survival outcomes in the non-metastatic setting of colorectal cancer. Further studies with a larger sample size are needed to validate the correlation of survival to the specific stage and anatomic location.

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