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Introduction

Colorectal cancer remains a significant public health concern, with its incidence steadily rising worldwide. Despite notable strides in treatment modalities, predicting disease progression and tailoring therapeutic approaches remains a challenge. In this context, identifying reliable and simple prognostic factors is crucial for optimizing disease outcomes.

Aims & Methods

The aim of this study was to investigate the predictive and prognostic value of platelet-to-lymphocyte ratio (PLR). We conducted a retrospective and descriptive study including patients diagnosed with primary colon or rectal cancer, over an 8-year period [January 2014-June 2022]. Patient demographics, inflammatory markers, tumor characteristics, treatment and follow-up data were collected. Baseline PLR was calculated for each patient. Data were entered and analyzed by SPSS software version 26.

Results

Eighty-four patients were included, with a mean age at disease diagnosis of 60 ± 12 years and a sex ratio M/F=1.89. The median level of PLR was 169.80 [123.1-269.06]. Smoker patient have significantly higher PLR (p=0.01) as well as for patients with older age at diagnosis (Pearson p=0.001, r=0.35). No significant association was noted of PLR neither with family history of colorectal cancer (p= 0.47), nor gender (p=0.69), nor tumor localization (p=0.15). For biological data, anemia and hypoalbuminemia were significantly associated with a higher level of PLR (p=0.01 and p=0.001 respectively). Regarding treatment, neither primary surgery, nor adjuvant chemotherapy were associated with PLR (p=0.36 and p= 0.97 respectively). However, increased PLR was significantly associated with overall survival (p=0.001). Area under the receiver operating characteristic curve analysis showed that higher PLR was predictive of a shorter progression-free survival (AUROC = 0.706). The optimal cutoff value was 163.12 (sensitivity, 80%; specificity, 59%). A total of 48 (57%) patients had a PLR above this threshold. These patients presented more frequently with bowel obstruction (23% vs 6%, p=0.03). They also had a higher carcinoembryonic antigen rates (p=0.007). Advanced TNM stage 3 or 4 was more common in patients with PLR above this threshold and thus, neoadjuvant chemotherapy was more indicated in this group (29% vs 11%; p=0.04). Overall, disease recurrence was similar for PLR above and below 163.12 (p=0.12).

Conclusion

Our study demonstrated that PLR has a good predictive value of progression-free survival connected with clinicopathological parameters in patients with colorectal cancer. It is a valuable tool for a simple prognostic assessment during colorectal cancer, contributing to a more personalized treatment decisions.

PLATELETS TO LYMPHOCYTES RATIO: A PROGNOSTIC INFLAMMATION-BASED FACTOR IN COLORECTAL CANCER

Wafa Khemiri 1, Myriam Ayari 1, Amira Chehaider 1, Mohamed Hedi Douggui 1, Jomni Mohamed Taieb 1

1 FSI Hospital, La Marsa, Tunisia

Conference

UEG Week Vienna 2024

Topics

Colorectal

Submission format

Abstract

Session

LOWER GI (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Colorectal cancer (CRC) remains a significant public health concern, with its incidence steadily rising worldwide. Despite notable strides in treatment modalities, predicting disease progression and tailoring therapeutic approaches remains a challenge. In this context, identifying reliable and simple prognostic factors is crucial for optimizing disease outcomes.

Aims & Methods

The aim of this study was to investigate the predictive and prognostic value of C-reactive protein-to-albumin ratio (CAR) in CRC. We conducted a retrospective and descriptive study including patients diagnosed with primary colon or rectal cancer, over an 8-year period [January 2014-June 2022]. Patient demographics, inflammatory markers, tumor characteristics, treatment and follow-up data were collected. Baseline CAR was calculated for each patient. Data were entered and analyzed by SPSS software version 26.

Results

Sixty-five patients were included, with a mean age at disease diagnosis of 61 ± 14 years and a sex ratio M/F=1.82. The median level of CAR was 0.4 [0.1-1.3]. No significant association was noted of CAR neither with age of disease onset (p=0.26), nor gender (p=0.86), nor smoking (p=0.88) nor family history of CRC (p= 0.54). For biological data, high levels of carcinoembryonic antigen and CA19-9 were significantly associated with a higher level of CAR (p=0.002 and p=0.01 respectively). We noted a significant association between lower levels of CAR and hematochezia (p=0.01) and so, rectal tumors were associated with lower levels of CAR compared with colonic tumors (26.2 vs 36; p=0.05). Circumferential, stenoting and friable tumors with hemorrhagic appearance were significantly associated with higher CAR levels (p=0.01; p=0.001 and p=0.01 respectively). We noted a significant association between high levels of CAR and metastases (50.1 vs 29.8; p=0.002) and mainly hepatic metastases (p=0.004). Regarding treatment, neither primary surgery nor urgent surgery nor adjuvant chemotherapy were associated with CAR (p=0.11; p=0.12 and p=0.85 respectively). However, an increased CAR was significantly associated with early readmission within 30 days subsequent to surgery (41.3 vs 26.7; p=0.01). Lower overall survival was associated with higher CAR rates (38.8 vs 29; p=0.04). Area under the receiver operating characteristic curve analysis showed that higher CAR was predictive of a shorter progression-free survival (AUROC = 0.65). The optimal cutoff value was 0.3 (sensitivity, 70%; specificity, 62%). A total of 36 (55%) patients had a CAR above this threshold. These patients presented more frequently with lymphopenia (p=0.03) and higher carcinoembryonic antigen rates (p=0.02). We noted no association between advanced TNM stage 3 or 4 and CAR levels, regardless of this threshold (p=0.36), and overall disease recurrence was similar for CAR above and below 0.3 (p=0.46).

Conclusion

C-reactive protein-to-albumin ratio is a strong predictor of progression-free survival and is associated with clinicopathological factors in CRC. It serves as a valuable tool for straightforward prognostic assessment, aiding in more personalized treatment decisions.

IMPACT OF C-REACTIVE PROTEIN-TO-ALBUMIN RATIO ON PROGNOSIS IN COLORECTAL CANCER

Wafa Khemiri 1, Myriam Ayari 1, Sarah Ben Azzouz 1, Amira Chehaider 1, Mohamed Hedi Douggui 1, Mohamed Taieb Jomni 1

1 FSI Hospital, La Marsa, Tunisia

Conference

UEG Week Berlin 2025

Topics

Colorectal

Submission format

Abstract

Session

LOWER GI (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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Introduction

Colonoscopy is the gold standard of an optimal exploration of the colon. Complete colonoscopy stands as the cornerstone for detecting precancerous lesions and colorectal screening.

Aims & Methods

The aim of our study was to identify factors limiting the completeness of the colonoscopy. We retrospectively colonoscopy reports performed between August 2023 and April 2024. Colonoscopies performed under general anesthesia were excluded from our analysis. Demographics, clinical and endoscopic data were collected. We investigated predictive factors of incomplete examinations.

Results

In total, 400 performed colonoscopies were included. The mean age of the patients was 56.5 years ± 14.22 (ranging from 16 to 91 years) and a male-to-female ratio of 2. History of diabetes was present in 24% of patients, hypertension in 38% of patients, and 7.8% of patients had chronic inflammatory bowel disease. The predominant indications for colonoscopy were constipation in 29% of cases, digestive bleeding in 16.1% of cases, diarrhea in 11% of cases, anemia in 9% of cases, screening in 4.8% of cases, and anal fistula in 3.8% of cases. The cecum was intubated in 381 colonoscopies (79.8% of cases). Interruption of the endoscopic examination were attributed to various causes, including inadequate preparation (45.5%), poor tolerance (32.5%) and irreducible loops (13%). In univariate analysis, anemia (p=0.033), history of benign prostatic hyperplasia, tolerance (p=0.05), and poor preparation (assessed by the Boston Bowel Preparation Scale) (p<0.0001) were identified as associated factors to incomplete colonoscopy. Demographic characteristics, comorbidities, irritable bowel syndrome, body mass index, abdominal hernia, history of anterior abdominal surgery were not associated with incomplete examination. On multivariate analysis, poor tolerance (p<0.0001, OR= 2.45 95%IC: 1.667-3.672), colonic preparation (p<0.0001, OR= 4.04 95%IC: 2.384-6.845) were predictive factors of incomplete colonoscopies.

Conclusion

This study confirms the importance of addressing limiting factors of a complete colonoscopy to avoid rescheduling the procedure and to prevent its psychological impact and delay in management and economic burden. Adequate analgesia and improved preparation are necessary for successful cecal intubation.

PREDICTIVE FACTORS OF INCOMPLETE SEDATION-FREE COLONOSCOPY

Emna Chemkhi 1, Myriam Ayari 1, Meriem NCIR 1, Nesrine Krifa 1, Mohamed Hedi Douggui 1, Jomni Mohamed Taieb 1

1 Internal Security Forces Hospital La Marsa, Tunis, Tunisia

Conference

UEG Week Vienna 2024

Topics

Colorectal

Submission format

Abstract

Session

LOWER GI (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Digestive neuroendocrine tumors (DNETs) are rare and ubiquitous neoplasm of the digestive tract, with an incidence that is increasing significantly in recent years. Special AT-rich sequence-binding protein 2 (SATB2) and the homeotic transcription factor (CDX2) are markers of intestinal differentiation that may be involved in the in the topographic diagnosis of DNET and thus orientate towards the site of the primary NET.

Aims & Methods

The aim of our work was to evaluate the immunohistochemical expression of CDX2 and SATB2 in DNET according to the topography and the histoprognostic factors. We conducted a longitudinal and retrospective study including 39 DNETs. Epidemiological and anatomopathological data according to the 2019 WHO classification were studied. The study of CDX2 and SATB2 was performed by immunohistochemical method. Positivity was considered in the presence of a nuclear immunoreactivity greater than 10%.

Results

The mean age of patients diagnosed with DNETs was 51.4 years with a sex ratio M/F of 0.77. The predilection sites were the small intestine and the appendix, in 33.3% of cases each. CDX2 was expressed in 64% of DNETs. It was positive in 90-100% of small intestine, appendix and colon neuroendocrine neoplasms. SATB2 was expressed in 60% of DNETs. It was found in 100% of appendicular and colorectal neuroendocrine tumors. A weak staining was observed in 69% of small intestine neuroendocrine tumors. Gastric and pancreatic tumors pancreatic tumors did not express CDX2 nor SATB2. This variation in expression was statistically significant (p<0.001). Grade G1 tumors (67%) were in 70% CDX2+/SATB2+. Grade G2/G3 tumors (33%) were in 68% of cases SATB2- without significant difference. The pT1/pT2 DNET (n=19) were CDX2+/SATB2+ in 68%. The pT3/pT4 tumors (n=17) were CDX2- in 35% and SATB2- in 47% without significant difference. Lymph node and distant metastases were found in 28% and 14% of cases respectively. No statistically significant correlation was noted between CDX2 or SATB2 and the presence of lymph node metastases. However, the loss of SATB2 was significantly associated with the metastatic potential (p<0.001).

Conclusion

CDX2 and SATB2 are highly sensitive and relatively specific markers of the digestive tract. They would be useful in the topographic approach of neuroendocrine tumors of unknown origin.

STUDY OF INTESTINAL DIFFERENTIATION MARKERS (CDX2 AND SATB2) IN DIGESTIVE NEUROENDOCRINE NEOPLAMS

Neila Ines Ben Romdhane 1, Myriam Ayari 1, Amen Dhaoui 1, Amira Chehaider 1, Mohamed Hedi Douggui 1, Jomni Mohamed Taieb 1

1 Internal Security Forces Hospital La Marsa, Tunis, Tunisia

Conference

UEG Week Vienna 2024

Topics

Colorectal

Submission format

Abstract

Session

LOWER GI (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Colorectal cancer is one of the most frequent malignant tumors worldwide. With increasing use of prognostic biomarkers, molecularly stratified treatment of colorectal cancer is improving in clinical practice. However, identifying stable and easily detectable biomarkers for clinical use remains a challenge. Among these biomarkers, epigenetic changes, especially DNA methylation, are the most promising candidates for clinical practice. Prominent examples of such methylation markers are SEPTIN9, the Secretin Receptor (SCTR), and Engrailed Homeobox 1 (EN1). The methylation preferentially affects CpG islands within promoter regions of these genes. Aberrant methylation of CpG islands in the promoter region can be associated with the silencing of tumor suppressor genes and promotes tumorigenesis and tumor growth.

Aims & Methods

Our goal is to develop an innovative diagnostic tool for the reliable detection of malignant colon tissue based on the recognition of specific methylation patterns. This reporter system will detect hypermethylated genetic regions in vivo using luminescence. Suitable biomarkers for this approach will be identified by methylation profiling of colorectal carcinoma cell lines as well as organoids from patients with colorectal cancer.
Our reporter system consists of two constructs. The first construct, the key element of which is the methyl-binding domain of Methyl-CpG-binding domain protein 1 (MBD1), recognizes hypermethylated CpG islands that are frequently located within the promoter region. The second construct can bind with high specificity to the genomic region of interest via the sgRNA of a deadCas9. When the two components combine in close proximity, a SplitTEV protease induces the newly developed flipNluc luciferase. The emitted luminescence signal then detects the tumor in a highly specific manner and can be quantified. In addition, whole-genome bisulfite sequencing on colon carcinoma cell lines HCT116 and CaCo2 and organoids from colon biopsies were used to identify additional specific hypermethylated regions. The raw data was analyzed bioinformatically using Bismark and the R package DSS.

Results

We verified the functionality of our new assay by assessing the induction of the newly developed flipNLuc luciferase by the TEV protease. We detected a significant increase in luminescence, confirming the functionality of the luciferase. Thereafter, we validated the reporter system by analyzing the methylation marker genes EN1 and SCTR, which are typically hypermethylated in colorectal carcinoma. In particular, significantly increased luminescence was measured compared to the unmethylated housekeeping genes GAPDH and GPI. To optimize the sensitivity and specificity of our new detection system, additional genes with differentially methylated regions were identified during bioinformatic analysis of the sequencing data. Currently, we are adapting our reporter system to these newly identified genes to validate their potential role as new specific biomarkers.

Conclusion

Reliable DNA methylation biomarkers for clinical practice in the diagnosis of colorectal cancer are still limited. The developed method allows the highly specific identification of malignant tissue based on the detection of hypermethylated CpG islands. Furthermore, our method can be used for targeted screening for new methylation markers. By replacing the sgRNAs of deadCas9, our newly developed method is not limited to the detection of colon tumors and can be adapted to the diagnosis of other tumor entities.

A NOVEL BIOMARKER ASSAY FOR THE IDENTIFICATION OF COLORECTAL CANCER CELLS BASED ON SPECIFIC METHYLATION PATTERNS

Mathias Seubert 1, Barbara Volz 1, Deniz Tümen 1, Elisabeth Aschenbrenner 1, Claudia Kunst 1, Martina Müller-Schilling 1, Karsten Gülow 1

1 University Hospital Regensburg, Regensburg, Germany

Conference

UEG Week Copenhagen 2023

Topics

Colorectal

Submission format

Abstract

Session

PP 06 Other lower GI disorders (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Colorectal cancer: A single cell atlas

Ruggero De Maria Marchiano 1

1 Università Cattolica del Sacro Cuore, Rome, Italy

Event

UEG Week Vienna 2024

Topics

Colorectal Digestive Oncology Mechanisms & Personalised Medicine Pancreas

Session

Single-cell transcriptomics in disease pathogenesis

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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Introduction

Colorectal cancer (CRC) is a global health problem with high incidence and mortality rates. Although the incidence has decreased with the use of screening tests, the mortality rate is approximately 1,6 – 2,0 % per year. Recent studies have shown a steady increase in the incidence of early onset (<50 years) CRC compared to that of patients >50 years of age. Early-onset CRC cancer is reported to have a more progressive course and may have a genetic and epigenetic background. In this study, we aimed to investigate the disease characteristics and risk factors for colorectal cancer in patients <50 years old and compare with patients over 50 years of age.

Aims & Methods

Patients younger than 50 years, diagnosed with colorectal adenocarcinoma and followed in our hospitals' gastroenterology, oncology, or general surgery departments between January/2009 and June/2022 were included in this retrospective study. A total of 6102 patients’ files were examined. Among these, 1166 were under the age of 50, whilst 4936 were 50 years and older. Patients younger than 18 years, who had a previous history of CRC, a known familial CRC syndrome, who had synchronous tumors at the time of diagnosis or had in situ CRC were not included in the study. After applying the exclusion criteria, 989 patients were included in the under-50 age group. The comparison group consisted of 1009 patients randomly selected from a group of 4000 patients aged 50 years or older. Patients were divided into Group A (<50 years) and Group B (≥ 50 years) according to the age at diagnosis. Patients’ demographic characteristics, body mass index, history of cigarette smoking and alcohol use, presenting symptoms, history of H. pylori infection, co-morbidities and medications were recorded from the files. Tumour characteristics, localization, size, TNM stage, and treatment methods were also analyzed and the relationship with each other was examined comparatively.

Results

The results of 1998 patients included in the study are shown in Table 1. TNM stages and the duration of symptoms before the diagnosis were similar between the groups but the rate of stage 1 disease was higher in group B. The rates of metastatic disease and rectal cancer were higher in Group A, but statistically non-significant. Abdominal pain was significantly more frequent in Group A, while anemia was significantly more common in Group B. Patients in Group A had higher rates of IBD, family history of CRC, mucinous adenocarcinoma, poorly differentiated tumor, higher histological grade and higher microsatellite instability (MSI-H). Although perineural and lymphatic invasion rates were similar, vascular invasion was higher in group B.

Table1. Comparison of Patients in Group A and Group B

Variables	Group A (n)	Group B (n)	p value
Body Mass Index ≥30 kg/m²	110	198	p<0.01
Family history of CRC	137	130	p<0.05
History of Inflammatory Bowel Disease	16	7	p<0.01
Tumor grade-1	104	151	p<0.01
Mucinous adenocarcinoma	131	90	p<0.01
Poor differentiation	165	96	p<0.01
High histologic grade	116	65	p<0.01
Presence of vascular invasion	277	412	p<0.01
MSI-H	58	29	p<0.01

Conclusion

Our study revealed that Early-onset CRC is more frequently diagnosed at the metastatic stage, is characterized by a more common presence of mucinous cells, poorly differentiated histology, and microsatellite instability.

RISK FACTORS AND HISPATHOLOGICAL CHARACTERISTICS OF EARLY-ONSET COLORECTAL CANCER

Elif Sitre Koc 1, Arzu Tiftikçi 1, Özlem Er 2, Aziz Yazar 2, Nesliar Eser Kutsal 1, Cem Aygun 1, Süha Göksel 1, Ayşe Sibel Erdamar Çetin 1, Nurdan Tözün 1

1 Acibadem University School of Medicine, Istanbul, Turkey

2 Acibadem Univrsiry School of Medicine, Istanbul, Turkey

Conference

UEG Week Copenhagen 2023

Topics

Colorectal

Submission format

Abstract

Session

PP 06 Other lower GI disorders (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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