Colon Cancer Survival Is Associated With Decreasing Ratio of Metastatic to Examined Lymph Nodes

Purpose Colorectal cancer is the second leading cause of cancer deaths in the United States, with poor survival predicted by regional lymph node (LN) metastasis. The impact of LN ratio (LNR) on survival is unknown in this disease. Patients and Methods We analyzed data from Intergroup trial 0089 of adjuvant chemotherapy for stage II and III patients with colon cancer, in which all patients received fluorouracil-based therapy. Survival was similar for all arms of the study, allowing us to evaluate all patients together. End points included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariate analyses were performed on all patients and on groups according to LNR quartiles (LNR: < 0.05, 0.05 to 0.19, 0.2 to 0.39, and 0.4 to 1.0). Covariates included in the models were age, sex, tumor stage, grade, histology, number of positive LNs, number of LNs removed, and LNR. Results The median age was 63.7 years, and the median number of LNs removed was 11. In the multivariate analysis, LNR was a significant factor for OS, DFS, and CSS in patients with 10 to 15 LN and more than 15 LN removed but not for patients with less than 10 LN removed. Using quartiles, LNR maintained its significance for all three end points when patients were grouped by node status. Conclusion After curative resection for colorectal cancer, the LNR is an important prognostic factor and should be used in stratification schemes for future clinical trials investigating adjuvant treatments.

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Superpixel image segmentation of VISTA expression in colorectal cancer and its relationship to the tumoral microenvironment

Scientific Reports ◽

10.1038/s41598-021-96417-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dongling Wu ◽

Sean Hacking ◽

Taisia Vitkovski ◽

Mansoor Nasim

Keyword(s):

Colorectal Cancer ◽

Image Segmentation ◽

T Cell Activation ◽

Cell Activation ◽

Disease Free Survival ◽

Tumor Stage ◽

The United States ◽

Mutational Status ◽

Microsatellite Stability

AbstractColorectal cancer (CRC) is the third most common cause of cancer related death in the United States (Jasperson et al. in Gastroenterology 138:2044–2058, 10.1053/j.gastro.2010.01.054, 2010). Many studies have explored prognostic factors in CRC. Today, much focus has been placed on the tumor microenvironment, including different immune cells and the extracellular matrix (ECM). The present study aims to evaluate the role of V-domain immunoglobulin suppressor of T cell activation (VISTA). We utilized QuPath for whole slides image analysis, performing superpixel image segmentation (SIS) on a 226 patient-cohort. High VISTA expression correlated with better disease-free survival (DFS), high tumor infiltrative lymphocyte, microsatellite instability, BRAF mutational status as well as lower tumor stage. High VISTA expression was also associated with mature stromal differentiation (SD). When cohorts were separated based on SD and MMR, only patients with immature SD and microsatellite stability were found to correlate VISTA expression with DFS. Considering raised VISTA expression is associated with improved survival, TILs, mature SD, and MMR in CRC; careful, well-designed clinical trials should be pursued which incorporate the underlying tumoral microenvironment.

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Internet Interest in Colon Cancer following Chadwick Boseman’s Death (Preprint)

10.2196/preprints.27052 ◽

2021 ◽

Author(s):

Hiten Naik ◽

Maximilian Desmond Dimitri Johnson ◽

Michael Roger Johnson

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Screening ◽

The United States ◽

Colon Cancer Screening ◽

Black American ◽

Online Activity ◽

The Public ◽

Search Terms ◽

The Impact

BACKGROUND Compared to White Americans, Black Americans have greater incidence and mortality rates from colon cancer, but lower up-to-date screening rates. Chadwick Boseman was a prominent Black American actor who died of colon cancer on August 28, 2020. As announcements of celebrity diagnoses often result in an increased awareness of particular conditions, Boseman’s death may have resulted in greater online interest in colon cancer. OBJECTIVE The objective of this study was to quantify the impact Chadwick Boseman’s death on online search interest in colon cancer, and thereby identify an opportunity for healthcare providers to educate the public and advocate for higher risk groups. METHODS We used Google Trends (GT) and Wikipedia pageview analysis to assess the change in online activity related to colon cancer in the United States from two years prior to Chadwick’s death to three months following the announcement of his death. We used two of GT search topics (“colorectal cancer” and “colon cancer screening”) and fifteen search terms related to colon cancer screening, symptoms, diagnosis and risk factors. We forecasted what RSVs and number of pageviews would be expected if his death had not occurred, and compared this to what was observed. The forecasts were generated with 95% bootstrapped confidence intervals (CIs) using the ARIMA algorithm in R software. RESULTS GT’s observed RSVs for the topics “colorectal cancer” and “colon cancer screening” increased by as much as 598% and 707%, respectively, and were on average 121% (95% CI, 72%-193%) and 256% (95% CI, 35%-814%) greater than expected during the first three months following Boseman’s death. Ten out of fifteen search terms had mean observed RSVs significantly higher than expected within the first and second month following Boseman’s death. Three of the fifteen search terms (“colon cancer signs”, “colon cancer survival” and “colon cancer symptoms”) remained significantly greater than expected within the third month following August 28, 2020. Daily Wikipedia pageview volume during the two months following Boseman’s death was on average 1,979% (95% CI, 1,375%-2,894%) greater than expected. Altogether, it is estimated that this represented 547,354 (95% CI, 497,708-585,167) excess Wikipedia pageviews beyond what would be expected if Boseman’s death had not occurred. CONCLUSIONS There has been a significant increase in online activity related to colon cancer following Chadwick Boseman’s death. This reflects a heightened public awareness that can be leveraged to further educate the public, including the high-risk Black American subgroup. The magnitude and duration of increased Google searches and Wikipedia pageviews following Boseman’s death is unprecedented in the literature and future research will reveal if this translates to improved screening and detection rates for colon cancer.

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An overview of clinical and economic outcomes of U.S. veteran colorectal cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14689 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e14689-e14689

Author(s):

Onur Baser ◽

Elyse Fritschel ◽

Lu Li ◽

J Zhang ◽

Li Wang

Keyword(s):

Colorectal Cancer ◽

Health Care ◽

Colon Cancer ◽

Cancer Patients ◽

Disease Free Survival ◽

Health Care Expenditures ◽

The United States ◽

Economic Outcomes ◽

Health Administration ◽

Colorectal Cancer Patients

e14689 Background: Colorectal cancer is the second leading cause of cancer-related death in the United States. While studies have shown that conditions such as diabetes are associated with shorter disease-free survival in colon cancer patients, fewer U.S. Department of Veterans Affairs (VA)-specific studies have been conducted focusing on colorectal cancer outcomes (Centers for Disease Control and Prevention. Colorectal (colon) cancer. www.cdc.gov/cancer/colorectal. Extermann M. Interaction between comorbidity and cancer. Cancer Control. 2007; 14(1): 13-22). This study aimed to describe the comorbidity profile and economic outcomes of colorectal cancer patients in the VA population. Methods: A retrospective study of patients diagnosed with colorectal cancer during the study period of October 1, 2005 to September 30, 2010 was conducted using the Veterans Health Administration datasets. All colorectal cancer patients were identified using International Classification of Disease 9thRevision Clinical Modification (ICD-9-CM) diagnosis codes 153.xx and 154.xx. Descriptive statistics were calculated as means ± standard deviation (SD) and percentages using SAS version 9.3 software. Results: In diagnosed colorectal cancer patients (n=62,200), common comorbidities included hypertension (n=18,309, 29.44%) and diabetes (n=10,891, 17.51%). Other minor comorbidities included hyperlipidemia and benign neoplasm of the colon. The average Fecal Occult Blood Test result (found in 12.21% of colorectal cancer veterans) was 96.37. Outpatient services were utilized by 99.71% of colorectal cancer patients, followed by pharmacy (91.94%) and inpatient visits (31.15%). Costs for outpatient ($10,637, SD=$17,125), pharmacy ($2,704, SD=$9,773), and inpatient services ($16,032, SD=$53,078) contributed to follow-up health care expenditures. Conclusions: Despite frequent outpatient utilization, inpatient costs have the greatest impact on the considerable health care cost incurred by lung cancer veterans. The presence of comorbid conditions may further complicate colorectal cancer treatment, though further characterization requires further research.

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Colon Cancer Survival Is Associated With Increasing Number of Lymph Nodes Analyzed: A Secondary Survey of Intergroup Trial INT-0089

Journal of Clinical Oncology ◽

10.1200/jco.2003.05.062 ◽

2003 ◽

Vol 21 (15) ◽

pp. 2912-2919 ◽

Cited By ~ 720

Author(s):

T.E. Le Voyer ◽

E.R. Sigurdson ◽

A.L. Hanlon ◽

R.J. Mayer ◽

J.S. Macdonald ◽

...

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Proportional Hazards ◽

Disease Free Survival ◽

Cox Proportional Hazards ◽

Rank Test ◽

End Points ◽

Intergroup Trial ◽

The Impact

Purpose: To determine the relationship, in patients with adenocarcinoma of the colon, between survival and the number of lymph nodes analyzed from surgical specimens. Patients and Methods: Intergroup Trial INT-0089 is a mature trial of adjuvant chemotherapy for high-risk patients with stage II and stage III colon cancer. We performed a secondary analysis of this group with overall survival (OS) as the main end point. Cause-specific survival (CSS) and disease-free survival were secondary end points. Rates for these outcome measures were estimated using Kaplan-Meier methodology. Log-rank test was used to compare overall curves, and Cox proportional hazards regression was used to multivariately assess predictors of outcome. Results: The median number of lymph nodes removed at colectomy was 11 (range, one to 87). Of the 3,411 assessable patients, 648 had no evidence of lymph node metastasis. Multivariate analyses were performed on the node-positive and node-negative groups separately to ascertain the effect of lymph node removal. Survival decreased with increasing number of lymph node involvement (P = .0001 for all three survival end points). After controlling for the number of nodes involved, survival increased as more nodes were analyzed (P = .0001 for all three end points). Even when no nodes were involved, OS and CSS improved as more lymph nodes were analyzed (P = .0005 and P = .007, respectively). Conclusion: The number of lymph nodes analyzed for staging colon cancers is, itself, a prognostic variable on outcome. The impact of this variable is such that it may be an important variable to include in evaluating future trials.

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Association of diabetes with colorectal cancer treatment and outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18112 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18112-e18112 ◽

Cited By ~ 1

Author(s):

Arjun Iyengar ◽

Heather Taffet Gold ◽

Joseph Nicholson ◽

Daniel Jacob Becker

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Treatment ◽

Meta Analysis ◽

Disease Free Survival ◽

Treatment Patterns ◽

Treatment Modalities ◽

Increased Risk ◽

Inconsistency Index ◽

The Impact

e18112 Background: Diabetes mellitus (DM) is associated with an increased incidence of colorectal cancer, but the impact of diabetes on colorectal cancer (CRC) prognosis and treatment patterns remains unknown. As outcomes in both CRC and DM have improved, appropriate co-management of the two diseases has become a priority to help patients live longer and healthier. Methods: A systematic search of PubMed, Embase, and CINAHL databases was performed to evaluate/assess the association of diabetes with colon cancer treatment patterns and outcomes, including recurrence rates (RR), disease free survival (DFS), colon cancer-specific (CSM) and all-cause mortality (ACM). We included English language peer-reviewed studies through November 2016 following the preferred reporting items of systematic reviews and meta-analyses (PRISMA) method. We applied STROBE quality criteria and conducted a random-effects meta-analysis. An inconsistency index (I2) was used to estimate the heterogeneity between studies. Results: After reviewing 2,611 reports, 35 studies were included that described an association of DM with CRC treatment patterns or outcomes. A meta-analysis of 14 studies that assessed (ACM) among 146,129 patients demonstrated an increased risk for ACM for CRC patients with DM (OR 1.28, 95% CI 1.16-1.42, I2 = 80%, P < .00001). No statistical significance was found in comparing 4 studies that looked at CSM (OR 0.91, 95% CI .72-1.14, I2 = 89%, P = 0.42). Analysis of 4 studies that assessed DFS found lower DFS in patients with DM (OR 1.75, 95% CI 1.33-2.31, I = 3%, P < .0001). Aggregating 3 studies that evaluated RFS demonstrated no clear association of DM and RFS(OR 1.12, CI 95% 0.91-1.38, I = 64%, P = .27). No consistent treatment discrepancies were noted in 6 studies that assessed the impact of DM on various CRC treatment modalities (receipt of surgery, chemotherapy, radiation). Conclusions: CRC patients with diabetes are at a greater risk for ACM and have worse DFS compared to those without DM. Analysis was limited due to study heterogeneity. We did not find consistent evidence that CRC is treated differently in patients with DM. Further study is warranted to clarify the mechanism of poor outcomes in CRC patients with DM and to improve survival.

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Clinicopathological features and survival of colorectal cancer patients younger than 50 years: a retrospective comparative study

Journal of the Egyptian National Cancer Institute ◽

10.1186/s43046-019-0006-z ◽

2019 ◽

Vol 31 (1) ◽

Author(s):

Robabeh Ghodssi-Ghassemabadi ◽

Ebrahim Hajizadeh ◽

Shaghayegh Kamian ◽

Mahmood Mahmoudi

Keyword(s):

Colorectal Cancer ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Stage ◽

Clinicopathological Features ◽

Advanced Tumor Stage ◽

Cancer Specific Survival ◽

Younger Patients ◽

Advanced Tumor ◽

Poorly Differentiated

Abstract Background Colorectal cancer (CRC) is a disease of old age, but its incidence has been rising among younger population compared to older ones. Nevertheless, there is a controversy over survival of younger patients compared to the older ones. Therefore, in the current study, we investigated the clinicopathological features and survival of the younger (< 50 years) versus older (≥ 50 years) CRC patients. Results The younger and older groups consisted of 39.4% and 60.6% of patients, respectively. Both age groups were comparable regarding the symptom presentation and duration, and pre-operative carcinoembryonic antigen (CEA). The younger patients were diagnosed with a higher proportion of poorly differentiated (14.7% vs. 8.3%; p < 0.001) and more advanced tumors (53.2% vs. 45.9%; p = 0.266). The rectum tumor site was significantly more common among the younger patients (p = 0.021). The overall survival (OS) (p = 0.278), the cancer-specific survival (CSS) (p = 0.233), and the disease-free survival (DFS) (p = 0.497) did not differ significantly between the two groups. Based on Cox regression model, elevated pre-operative CEA level (HR = 1.41; 95%CI of 1.01–1.97), advanced tumor stage (6.06; 95%CI of 3.03–12.15), and poorly differentiated tumor (HR = 1.69; 95%CI of 1.05–2.71) were associated with decreased survival. Conclusions The younger patients did not have poor prognosis compared to the older ones despite having an advanced tumor stage and a poor tumor differentiation.

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Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00581-9 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Jiao Wu ◽

Sai-Ching Jim Yeung ◽

Sicheng Liu ◽

Aiham Qdaisat ◽

Dewei Jiang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Weight Loss ◽

Cancer Patients ◽

Cancer Cell ◽

Cancer Progression ◽

Colorectal Cancer Patient ◽

Nutrition Support ◽

Immunodeficient Mice ◽

The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

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Clinical significance of kallikrein-related peptidase 7 (KLK7) in colorectal cancer

Thrombosis and Haemostasis ◽

10.1160/th08-07-0471 ◽

2009 ◽

Vol 101 (04) ◽

pp. 741-747 ◽

Cited By ~ 26

Author(s):

Konstantina Mathioudaki ◽

Panagiotis Prezas ◽

Dimitra Alexopoulou ◽

Eleftherios Diamandis ◽

Dimitris Xynopoulos ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Stratum Corneum ◽

Human Tissue ◽

Serine Proteases ◽

Human Cancer ◽

Disease Free Survival ◽

Normal Colonic Mucosa ◽

Tissue Kallikrein ◽

Human Cancer Cell Lines

SummaryHuman tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohisto-chemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RTPCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.

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Public Interest and Behavior Change in the United States Regarding Colorectal Cancer Following the Death of Chadwick Boseman: Infodemiology Investigation of Internet Search Trends Nationally and in At-Risk Areas (Preprint)

10.2196/preprints.29387 ◽

2021 ◽

Author(s):

Nicholas B Sajjadi ◽

Kaylea Feldman ◽

Samuel Shepard ◽

Arjun K Reddy ◽

Trevor Torgerson ◽

...

Keyword(s):

Colorectal Cancer ◽

United States ◽

At Risk ◽

Colon Cancer ◽

Public Interest ◽

Black Population ◽

The United States ◽

American Cancer Society ◽

Cancer Society ◽

Search Volume

BACKGROUND Colorectal cancer (CRC) has the third highest cancer mortality rate in the United States. Enhanced screening has reduced mortality rates; however, certain populations remain at high risk, notably African Americans. Raising awareness among at-risk populations may lead to improved CRC outcomes. The influence of celebrity death and illness is an important driver of public awareness. As such, the death of actor Chadwick Boseman from CRC may have influenced CRC awareness. OBJECTIVE We sought to assess the influence of Chadwick Boseman’s death on public interest in CRC in the United States, evidenced by internet searches, website traffic, and donations to prominent cancer organizations. METHODS We used an auto-regressive integrated moving average model to forecast Google searching trends for the topic “Colorectal cancer” in the United States. We performed bivariate and multivariable regressions on state-wise CRC incidence rate and percent Black population. We obtained data from the American Cancer Society (ACS) and the Colon Cancer Foundation (CCF) for information regarding changes in website traffic and donations. RESULTS The expected national relative search volume (RSV) for colorectal cancer was 2.71 (95% CI 1.76-3.66), reflecting a 3590% (95% CI 2632%-5582%) increase compared to the expected values. With multivariable regression, the statewise RSV increased for each percent Black population by 1.09 (SE 0.18, <i>P</i><.001), with 42% of the variance explained (<i>P</i><.001). The American Cancer Society reported a 58,000% increase in CRC-related website traffic the weekend following Chadwick Boseman’s death compared to the weekend before. The Colon Cancer Foundation reported a 331% increase in donations and a 144% increase in revenue in the month following Boseman’s death compared to the month prior. CONCLUSIONS Our results suggest that Chadwick Boseman’s death was associated with substantial increases in awareness of CRC. Increased awareness of CRC may support earlier detection and better prognoses.

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Colorectal Liver Metastasis

10.2310/7800.16064 ◽

2019 ◽

Author(s):

Brian E Kadera ◽

Michael D’Angelica

Keyword(s):

Colorectal Cancer ◽

Surgical Techniques ◽

Disease Free Survival ◽

Hepatic Arterial Infusion ◽

The United States ◽

Surgical Approaches ◽

Portal Vein Ligation ◽

Arterial Infusion ◽

Liver Remnant ◽

Infusion Chemotherapy

Metastatic colorectal cancer isolated to the liver is a common clinical presentation in the United States, occurring in an estimated 50,000 patients per year. Unlike most stage IV malignancies, surgery is an effective mainstay of therapy. In the past several decades, novel surgical approaches, improved systemic chemotherapy, and locoregional therapies such as ablation and hepatic arterial infusion chemotherapy have broadened the indications for resection. At the same time, advances in perioperative care and adoption of parenchymal-sparing surgical techniques have lowered the perioperative mortality of liver resection to approximately 1%. Surgical cure is possible and using 10-year disease-free survival as a definition, this can be achieved in approximately 20 to 30% of well-selected patients. The majority of patients recur; thus, active surveillance is appropriate to identify patients for potential salvage therapy, including in some cases repeat resections and/or ablation, which is associated with prolonged survival and potential cure. More research is needed in biomarker drivers of prognosis, as there are few reliable clinicopathologic indicators to identify those in whom surgery will not benefit. This review contains 7 figures, 7 tables, and 90 references. Key Words: colorectal cancer, FOLFOX, FOLFIRI, hepatic arterial infusion, hepatic resection, liver remnant, microwave ablation, portal vein ligation, ALPPS

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