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LIVER FIBROSIS DRIVES COLORECTAL CANCER DEVELOPMENT: A RETROSPECTIVE ANALYSIS IN 1145 METABOLIC SUBJECTS

LUCILLA CRUDELE 1, Carlo De Matteis 1, Fabio Novielli 1, Stefano Petruzzelli 1, Marica Cariello 1, Raffaella Maria Gadaleta 1, Antonio Moschetta 1

Affiliations

1 Univeristy of Bari "Aldo Moro", Bari, Italy

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Abstract

Introduction

Liver steatosis represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumorigenic triggers, specifically in colorectal cancer (CRC) [1]. Fatty liver diagnosis challenges clinicians since it is clinically silent and may be complicated with liver fibrosis. Since liver biopsy is not feasible in all patients, non-invasive and point-of-care indexes have been proposed to detect liver steatosis and fibrosis [2].

Aims & Methods

We performed a retrospective analysis among 1145 metabolic subjects to reveal any condition that may predict and concur to CRC development during a 8-years period. Anthropometric and bio humoral parameters were recorded at time zero. Non-invasive liver fibrosis scores were calculated as follows: AAR=AST/ALT; FIB-4=(age x AST)/(platelet count x √ALT); mFIB-4=(10 x age x AST)/(platelet count x ALT); Forns=7.811 - 3.131 x ln(platelet count) + 0.781 x ln(GGT) + 3.467 x ln(age) - 0.014 x (total cholesterol); APRI= AST/Upper limit of normal values x 100/platelet count; AARPRI=AST/ALT/platelet count x 150. Comparisons were carried out by Student-T test (p-value <0.05 was considered significant) and ROC analysis was performed to assess cut-off values. Chi-square test was used to calculate the associated Odds Ratio (OR) with 95% confidence interval (CI).

Results

During a 8 years period, 28 patients (2.4%) developed CRC. No association between CRC development and visceral and general obesity was detected, while fasting plasma glucose was significantly higher and Vitamin D was significantly lower in patients who later were diagnosed with CRC, compared to those who did not develop cancer. We found that all non-invasive liver fibrosis scores significantly identified CRC-developer at time 0 (see Table). In ROC analysis, these scores also showed good sensitivity and specificity in predicting colon cancer (AAR AUC= 0.59, sensitivity 44% and specificity 78%; FIB-4 AUC= 0.74, sensitivity 84% and specificity 57%; mFIB-4 AUC=0.69, sensitivity 80% and specificity 53%; Forns AUC= 0.67, sensitivity 73% and specificity 54%; APRI AUC= 0.63, sensitivity 57% and specificity 75%; AARPRI AUC =0.64, sensitivity 44% and specificity 83%). We then calculated ORs for values above the ROC cut-offs finding that higher FIB-4 was associated with a 6-fold increased risk of developing CRC (95% CI=2.2-16.5), while mFIB-4 showed a OR=3.6 (95% CI=1.4-8.7), Forns OR was 3.1 (95% CI=1.3-7.9), APRI OR was 3.2 (95% CI=1.4-6.9) and AARPRI OR was 3 (95% CI=1.3-6.4).

	No Cancer (n=1117) mean ± SD	Colon cancer (n=28) mean ± SD	p-value
Fasting glucose (mg/dL)	100.8±29.1	119.5±49.8	0.0011
25-OH Vitamin D (pg/mL)	22.8±11.2	16.3±7.8	0.0099
AAR	0.8±0.3	1±0.5	0.0064
FIB-4	1.1±0.7	1.8±1	<0.0001
mFIB-4	2.2±1.5	3.3±2.3	0.0004
Forns	5.3±1.8	6.3±1.3	0.0039
APRI	0.3±0.2	0.5±0.4	0.0003
AARPRI	0.6±0.3	0.8±0.5	0.0011

Conclusion

These findings support the hypothesis that liver steatosis and fibrosis may play a role in the clinical background of CRC and bring to light the fascinating possibility of a reversed gut-liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of liver fibrosis may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.

References

[1] Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:1625–38. https://doi.org/10.1056/NEJMoa021423.
[2] Hernandez Roman J, Siddiqui MS. The role of noninvasive biomarkers in diagnosis and risk stratification in nonalcoholic fatty liver disease. Endocrinol Diabetes Metab 2020;3:e00127. https://doi.org/10.1002/edm2.127.

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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SAFETY AND EFFICACY OF LOW POWER PURE-CUT HOT SNARE POLYPECTOMY FOR NONPEDUNCULATED COLORECTAL POLYPS 10 TO 14 MM IN SIZE: A MULTICENTER RETROSPECTIVE STUDY

Hidenori Kimura 1, Kazunori Takada 2, Kenichiro Imai 2, Yoshihiro Kishida 2, Sayo Ito 2, Kinichi Hotta 2, Takayuki Imai 1, Yukihiro Morita 1, Shigeki Bamba 1, Osamu Inatomi 1, Hiroyuki Ono 2, Akira Andoh 1

Affiliations

1 Shiga University of Medical Science, Shiga, Japan

2 Shizuoka Cancer Center, Shizuoka, Japan

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Abstract

Introduction

Cold snare polypectomy (CSP) for polyps 10-14 mm is unsatisfactory, with higher rates of unclear/positive histologic margins compared to small polyps,¹ which is similar for CSP with submucosal injection.² Therefore, hot snare polypectomy (HSP) or endoscopic mucosal resection (EMR) has been widely performed for polyps measuring ≥10 mm.³ However, these procedures often cause adverse events such as delayed bleeding and perforation due to deep thermal injury related to the use of electrocautery.⁴ A recent large-scale study reported a low incidence (0.9%) of invasive cancer in 10-19 mm colorectal polyps.⁵ Therefore, the development of less invasive therapeutic options for this size category is demanding.
Thus, we have developed HSP with low power pure-cut current (LPPC-HSP), a polypectomy technique with low power, low voltage, and no coagulation current (UMIN Clinical Trials Registry; UMIN000037678). This method uses pure-cut current and reduces the power of electrocautery, expecting less deep thermal damage compared with conventional HSP with blend or coagulation current, resulting in a lower risk of perforation and bleeding. This study aimed to evaluate the efficacy and safety of LPPC-HSP for colorectal polyps 10 to 14 mm, compared with conventional EMR.

Aims & Methods

In this multicenter, retrospective, observational study, records of patients who underwent EMR or LPPC-HSP for nonpedunculated colorectal polyps 10 to 14 mm at two Japanese institutions between January 2021 and March 2022 were evaluated consecutively. EMR was performed with blend cut current (Endocut Q; effect 3, time interval 2, time duration 2), while LPPC-HSP with a low power pure-cut current (Autocut; effect 1, 10 W in VIO300D or Autocut; effect 0.4 [Pmax 13 W] in VIO3). We analyzed the treatment outcomes of the two techniques using propensity score matching to reduce selection bias. The following variables expected to affect treatment outcomes were selected: age, sex, polyp size, morphology, lesion location, endoscopists (experienced endoscopists or gastrointestinal fellows), and antithrombotic agents. R0 resection was defined as en bloc resection with histologically tumor-free margins.

Results

We retrospectively enrolled 203 EMR (168 patients, 203 lesions) and 208 LPPC-HSP (169 patients, 208 lesions) cases. After propensity score matching, the baseline characteristics between the groups were comparable, with 131 pairs. The en bloc and R0 resection rates were not significantly different between EMR and LPPC-HSP groups (93.9% vs. 96.9%, P=0.38; 90.8% vs. 91.6%, P=1.00). The vertical margin was negative in all lesions except one in the EMR group. Immediate bleeding requiring hemostasis was observed in 10.7% of cases in the EMR group versus 2.3% in the LPPC-HSP group (P=0.010). The rates of delayed bleeding and perforation didn’t differ between the groups (0% vs. 0.8%, P=1.00; 0% vs. 0%).

Table 1. Baseline characteristics and treatment outcomes after propensity score matching
Baseline characteristics	EMR n=131	LPPC-HSP n=131	P value	standardized difference	Treatment outcomes	EMR n=131	LPPC-HSP n=131	P value
Age, years (interquartile range)	72 (67-76)	72 (68-78)	0.29	0.105	En bloc resection (%)	123 (93.9)	127 (96.9)	0.38
Male sex (%)	91 (70)	96 (73)	0.59	0.085	R0 resection (%)	119 (90.8)	120 (91.6)	1.00
Lesion size, mm (interquartile range)	10 (10-12)	10 (10-12)	0.93	0.017	Immediate bleeding (%)	14 (10.7)	3 (2.3)	0.01
Location right colon/left colon/rectum (%)	61 (47) / 53 (41) / 17 (13)	63 (48) / 53 (41) / 15 (12)	0.95	0.049	Delayed bleeding (%)	0 (0)	1 (0.8)	1.00
Morphology 0-Is/0-IIa (%)	89 (68) / 42 (32)	87 (66) / 44 (34)	0.90	0.033	Perforation (%)	0 (0)	0 (0)	N/A
Antithrombotic agents (%)	24 (18)	35 (27)	0.14	0.202
Gastrointestinal fellows performed (%)	42 (32)	44 (34)	0.90	0.033

Conclusion

LPPC-HSP showed treatment outcomes comparable to conventional EMR, with fewer adverse events. These results suggest that this technique is a safe and effective treatment for nonpedunculated colorectal polyps 10 to 14 mm.

References

1. Hirose R, Yoshida N, Murakami T, et al. Histopathological analysis of cold snare polypectomy and its indication for colorectal polyps 10-14 mm in diameter. Dig Endosc 2017;29:594-601.
2. Yabuuchi Y, Imai K, Hotta K, et al. Efficacy and safety of cold-snare endoscopic mucosal resection for colorectal adenomas 10 to 14 mm in size: a prospective observational study. Gastrointest Endosc 2020;92:1239-1246.
3. Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017;49:270-297.
4. Oka S, Tanaka S, Kanao H, et al. Current status in the occurrence of postoperative bleeding, perforation and residual/local recurrence during colonoscopic treatment in Japan. Dig Endosc 2010;22:376-380.
5. Parsa N, Ponugoti P, Broadley H, et al. Risk of cancer in 10 - 19 mm endoscopically detected colorectal lesions. Endoscopy 2019;51:452-457.

Disclosure

Authors declare no Conflict of Interests for this study.

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

More Like This:

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Santiago García-López

DECIPHERING THE PRODROME OF INFLAMMATORY BOWEL DISEASE UP TO 10 YEARS BEFORE DISEASE ONSET BY MASSIVELY PARALLEL SEROLOGY

Thomas Vogl

New kids on the block: Novel advanced therapies

Sebastian Zeissig

LIVER FIBROSIS DRIVES COLORECTAL CANCER DEVELOPMENT: A RETROSPECTIVE ANALYSIS IN 1145 METABOLIC SUBJECTS

Raffaella Maria Gadaleta

SAFETY AND EFFICACY OF LOW POWER PURE-CUT HOT SNARE POLYPECTOMY FOR NONPEDUNCULATED COLORECTAL POLYPS 10 TO 14 MM IN SIZE: A MULTICENTER RETROSPECTIVE STUDY

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