THE RELATIONSHIP BETWEEN HISTOPATHOLOGICAL FINDDINGS OF HEPATIC METASTATIC FOCI OF THE COLORECTAL CANCER AND PROGNOSIS AFTER HEPATECTOMY-A CLINICAL STUDY-

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

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A Student’s Guide to the Classification and Operationalization of Variables in the Conceptualization and Design of a Clinical Study: Part 1

Indian Journal of Psychological Medicine ◽

10.1177/0253717621994334 ◽

2021 ◽

Vol 43 (2) ◽

pp. 177-179 ◽

Cited By ~ 1

Author(s):

Chittaranjan Andrade

Keyword(s):

Clinical Study ◽

Significant Relationship ◽

Research Experience ◽

Process Variables ◽

Know How ◽

Independent Variables ◽

Cause And Effect ◽

Confounding Variables ◽

Dependent Variables ◽

The Relationship

Students without prior research experience may not know how to conceptualize and design a study. This article explains how an understanding of the classification and operationalization of variables is the key to the process. Variables describe aspects of the sample that is under study; they are so called because they vary in value from subject to subject in the sample. Variables may be independent or dependent. Independent variables influence the value of other variables; dependent variables are influenced in value by other variables. A hypothesis states an expected relationship between variables. A significant relationship between an independent and dependent variable does not prove cause and effect; the relationship may partly or wholly be explained by one or more confounding variables. Variables need to be operationalized; that is, defined in a way that permits their accurate measurement. These and other concepts are explained with the help of clinically relevant examples.

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Oncological evaluation in the perioperative period using cfDNA with BRAF V600E mutation in patients with colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-92795-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Keita Tanaka ◽

Yoichiro Yoshida ◽

Teppei Yamada ◽

Takaomi Hayashi ◽

Hideki Shimaoka ◽

...

Keyword(s):

Colorectal Cancer ◽

Perioperative Period ◽

Radical Resection ◽

Braf V600e ◽

Tumor Diameter ◽

Prognostic Information ◽

A Prospective Study ◽

Digital Polymerase Chain Reaction ◽

The Relationship

AbstractThe detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of CRC.

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The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-019-07931-6 ◽

2019 ◽

Vol 26 (13) ◽

pp. 4397-4404 ◽

Cited By ~ 10

Author(s):

Hester C. van Wyk ◽

Antonia Roseweir ◽

Peter Alexander ◽

James H. Park ◽

Paul G. Horgan ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Evaluation Method ◽

Venous Invasion ◽

Staging System ◽

Consensus Conference ◽

Tumor Budding ◽

Inflammatory Cell Infiltrate ◽

Cancer Specific Survival ◽

The Relationship

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC.

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