scholarly journals Translational Potential of MicroRNAs for Preoperative Staging and Prediction of Chemoradiotherapy Response in Rectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1545 ◽  
Author(s):  
Machackova ◽  
Prochazka ◽  
Kala ◽  
Slaby

Abstract: Colorectal cancer is the third most common cancer and the second cause of cancer-related deaths. Rectal cancer presents roughly one-third of all colorectal cancer cases and differs from it on both anatomical and molecular levels. While standard treatment of colon cancer patients is radical surgery, rectal cancer is usually treated with pre-operative chemoradiotherapy followed by total mesorectal excision, which requires precise estimation of TNM staging. Unfortunately, stage evaluation is based solely on imaging modalities, and they often do not correlate with postoperative pathological findings. Moreover, approximately half of rectal cancer patients do not respond to such pre-operative therapy, so they are exposed to its toxic effects without any clinical benefit. Thus, biomarkers that could precisely predict pre-operative TNM staging, and especially response to therapy, would significantly advance rectal cancer treatment—but till now, no such biomarker has been identified. In cancer research, microRNAs are emerging biomarkers due to their connection with carcinogenesis and exceptional stability. Circulating miRNAs are promising non-invasive biomarkers that could allow monitoring of a patient throughout the whole therapeutic process. This mini-review aims to summarize the current knowledge on miRNAs and circulating miRNAs involved in the prediction of response to treatment and pre-operative staging in rectal cancer patients.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3566-3566
Author(s):  
D. S. Lo ◽  
A. Pollett ◽  
S. Gallinger ◽  
L. L. Siu ◽  
R. L. Burkes

3566 Background: Tumor nodules are occasionally found in adjacent mesentery of colorectal cancer specimens, but their prognostic significance is unclear. According to the TNM staging system, mesenteric nodules are classified as part of T or N categories, but clinically they are regarded to reflect a worse prognosis, more like M1. We investigated the clinical significance of mesenteric tumor nodules. Methods: We reviewed 786 patients with stage III colorectal cancer referred between 1995 and 1999. We standardized TNM staging by assigning N status based on number of definite lymph nodes. Mesenteric nodules were considered separately and not assigned to T or N categories. Survival analyses were performed. Results: Mesenteric tumor nodules were found in 116 patients (14.8%); 48 with colon cancer (41.4%) and 68 rectal cancer (58.6%). Mean age at surgery was 62.8±1.0 yrs (SE), and the male: female ratio was 1.2. All tumors were adenocarcinomas with an average size of 4.3±0.1 cm, and the majority were moderately differentiated. Resection margins were clear except in 7 cases. With respect to high risk features, 6 cases (5.2%) had bowel perforation, 12 (10.3%) obstructive symptoms, 41 (35.3%) lymphovascular invasion, and 11 (9.5%) were T4 lesions. Adjuvant chemotherapy was given to 84.8% of colon cancer patients. Two (2.9%) rectal cancer patients received neoadjuvant chemo-radiation, and 63 (92.6%) received adjuvant therapy; chemotherapy, radiation or both. In the cohort with mesenteric nodules, the median time to progression was 23.1 months; the median 5-yr disease free survival was 35%; and the median overall survival (OS) was 47.9 months, with 44% OS at 5 yrs. After TNM standardization, 19 (16.4%) patients were down-staged to either stage I or II, and their 5-yr OS was 60% (SEER Stage II 5 yr survival 82.5%). In the remaining cohort-patients with stage III disease after standardization, the 5-yr OS was 40% (SEER 5yr survival Stage IIIc 44.3%; Stage IV 8.1%). Conclusions: In comparison to SEER survival data, the presence of mesenteric nodules appears to worsen prognosis of any T/N0 disease to that of overall stage III disease. Patients with mesenteric nodules in the setting of any T/N1+ disease had prognosis similar to that of stage IIIC disease, but their prognosis was better than M1 disease. No significant financial relationships to disclose.


Author(s):  
Claudia Reali ◽  
Gabriele Bocca ◽  
Ian Lindsey ◽  
Oliver Jones ◽  
Chris Cunningham ◽  
...  

AbstractAccurate preoperative staging of colorectal cancers is critical in selecting patients for neoadjuvant therapy prior to resection. Inaccurate staging, particularly understaging, may lead to involved resection margins and poor oncological outcomes. Our aim is to determine preoperative imaging accuracy of colorectal cancers compared to histopathology and define the effect of inaccurate staging on patient selection for neoadjuvant treatment(NT). Staging and treatment were determined for patients undergoing colorectal resections for adenocarcinomas in a single tertiary centre(2016–2020). Data were obtained for 948 patients. The staging was correct for both T and N stage in 19.68% of colon cancer patients. T stage was under-staged in 18.58%. At resection, 23 patients (3.36%) had involved pathological margins; only 7 of which had been predicted by pre-operative staging. However, the staging was correct for both T and N stage in 53.85% of rectal cancer patients. T stage was understaged in 26.89%. Thirteen patients had involved(R1)margins; T4 had been accurately predicted in all of these cases. There was a general trend in understaging both the tumor and lymphonodal involvement (T p < 0.00001 N p < 0.00001) causing a failure in administrating NT in 0.1% of patients with colon tumor, but not with rectal cancer. Preoperative radiological staging tended to understage both colonic and rectal cancers. In colonic tumours this may lead to a misled opportunity to treat with neoadjuvant therapy, resulting in involved margins at resection.


2019 ◽  
Author(s):  
Maurits P. Engbersen ◽  
Max J. Lahaye ◽  
Regina G.H. Beets-Tan

Imaging increasingly plays an important role in selecting the most optimal treatment for patients with colon and rectal cancer. While in colon cancer, computed tomography (CT) remains the modality of choice for local and distant staging, in patients with rectal cancer magnetic resonance imaging (MRI) is the main modality and mandatory for local staging. Endoluminal rectal ultrasound (ERUS) is the preferred staging method for superficial rectal tumors. This chapter addresses the current role of various imaging modalities in colorectal tumor staging. This review contains 4 figures and 50 references. Key words: Preoperative imaging, Colorectal cancer, Magnetic resonance imaging, Diffusion weighted MRI, Computed tomography, Mesorectal fascia, TNM staging, Treatment stratification


2019 ◽  
Author(s):  
Maurits P. Engbersen ◽  
Max J. Lahaye ◽  
Regina G.H. Beets-Tan

Imaging increasingly plays an important role in selecting the most optimal treatment for patients with colon and rectal cancer. While in colon cancer, computed tomography (CT) remains the modality of choice for local and distant staging, in patients with rectal cancer magnetic resonance imaging (MRI) is the main modality and mandatory for local staging. Endoluminal rectal ultrasound (ERUS) is the preferred staging method for superficial rectal tumors. This chapter addresses the current role of various imaging modalities in colorectal tumor staging. This review contains 4 figures and 50 references. Key words: Preoperative imaging, Colorectal cancer, Magnetic resonance imaging, Diffusion weighted MRI, Computed tomography, Mesorectal fascia, TNM staging, Treatment stratification


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.


2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Georg Lurje ◽  
Marc Schiesser ◽  
Andreas Claudius Hoffmann ◽  
Paul Magnus Schneider

Since their introduction more than 50 years by Engell, circulating tumor cells (CTCs) have been evaluated in cancer patients and their detection has been correlated with clinical outcome, in esophageal, gastric, and colorectal cancer. With the availability of refined technologies, the identification of CTCs from peripheral blood is emerging as a useful tool for the detection of malignancy, monitoring disease progression, and measuring response to therapy. However, increasing evidence suggests a variety of factors to be responsible for disease progression. The analysis of a single CTC marker is therefore unlikely to accurately predict progression of disease with sufficient resolution and reproducibility. Here we discuss the current concept of CTCs, summarize the available techniques for their detection and characterization, and aim to provide a comprehensive update on the clinical implications of CTCs in gastrointestinal (GI) malignancies.


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]


2021 ◽  
Vol 3 (3) ◽  
pp. 01-04
Author(s):  
Aliya Ishaq

Background: There is an evident change in the colorectal cancer demographic over the period. This change is more marked in the age distribution and location of the tumor. It has practical implications, in regards to develop cancer awareness programs and screening protocols. Keeping in view that Pakistan is one of the countries with a high number of the young population this study is carried out to make a comparative analysis of this trend in our population. Material and methods: Colorectal cancer patients presented in Sindh Institute of urology and transplantation from January 2011 till December 2020 was reviewed retrospectively. All patients were divided into two groups, Group A young age population and Group B old age population. Subgroup analysis of study period was performed to check the progressive change in the trend of stage and clinical characteristics of colorectal cancer patients. Data reviewed from the patient’s files and collected as per Proforma requirement. Result: Total of 612 patients with colorectal cancer presented between 2011 till 2020.Among these patients 243 (39.7%) presented between January 2011 till December 2015. Patients age 50 years and younger were 410 (66.8%). Results showed a statistically significant association between and patient’s age and location of tumor such that left-sided colonic cancer and rectal cancer were more common in the young population. Subgroup analysis according to the study period showed that there is a change in the trend of disease presentation. Right-sided colonic cancer presentation decreased in the younger population over the period while simultaneously left-sided colonic cancer and rectal cancer presentation increased. Conclusion: The incidence of left-sided colonic and rectal cancer has been increased in the younger population over the specified period while there was no association between right-sided colon cancer and age noticed.


2020 ◽  
Author(s):  
Barbora Zwinsová ◽  
Vyacheslav Petrov ◽  
Martina Hrivňáková ◽  
Stanislav Smatana ◽  
Lenka Micenková ◽  
...  

Abstract BackgroundLong-term dysbiosis of the gut microbiome has a significant impact on the development, progression and the aggressiveness of colorectal cancer (CRC) and may explain part of the observed heterogeneity of the disease from phenotypic, prognostic and response to treatment perspectives. Although the shifts in gut microbiome in the normal-adenoma-carcinoma sequence have been described, the landscape of microbiome within CRC and its associations with clinical variables remain under-explored. ResultsWe performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually-normal mucosa and stool swabs of N=186 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variable and to derive tumour microbial subtypes.We identified new genera never previously associated with CRC tumour mucosa (Flavonifractor, Haemophilus, Howardella, Pseudomonas, Sutterella, Treponema 2) or CRC (Actinobacillus, Aggregatibacter, Bergeyella, Phocaeiola, Defluviitaleaceae UCG-011, Massilia, Tyzzerella 4). The bacteria residing on tumour-mucosa were dominated by genera belonging to (potential) oral pathogens. Based on tumour microbial profiles, we stratified CRC patients into three subtypes. The subtypes were significantly associated with prognostic factors such as tumor grade, primary tumour sidedness and TNM staging, with one subtype enriched in tumours with poor prognosis. Further, we inspected the associations of microbiome with clinical variables in a subtype-agnostic setting. The primary tumour-associated clinical variables predominantly correlated with tumour mucosal microbiome, while the presence of local and distant metastases was mostly associated with the stool microbiome.ConclusionsUnderstanding the interactions of the bacteria residing on tumour mucosa within different CRC tumour microbiome subtypes will help to better understand the underlying biological background of the heterogeneity of this disease. Indeed, the tumour microbiome is a possible source of additional integrative markers of CRC patients’ survival and prognosis. We found that CRC microbiome is strongly correlated with clinical variables, but these associations are dependent on the microbial environment (tumour mucosa, normal mucosa, stool). Our study thus identifies limitations of the usage of microbiome composition as marker of CRC progression, suggesting the need of combining several sampling sites (e.g. stool and tumour swabs).


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