Introduction

Colorectal cancer (CRC) patients commonly encounter anemia, with estimates indicating that up to 58% are affected and iron deficiency (ID) anemia being the most prevalent. This study aimed to compare the efficacy and safety of preoperative intravenous iron (IVI) with standard care (no iron or oral iron) in CRC patients with ID anemia.

Aims & Methods

We conducted a systematic search of the Cochrane Library, PubMed, Scopus, and Web of Science databases from inception to September 20, 2023, to identify studies comparing intravenous iron (IVI) versus standard care in colorectal cancer (CRC) patients with iron deficiency anemia. Pooled results were analyzed for changes in hemoglobin (Hb) levels from baseline, need for red blood cell (RBC) transfusions, mean number of RBC units transfused, overall survival (OS), disease-free survival (DFS), and complications.We evaluated randomized clinical trials using the Cochrane Risk of Bias 2 tool and observational studies using the Newcastle Ottawa Scale. Statistical analysis was performed using Revman software Version 5.4.1.

Results

We analyzed data from 11 studies, encompassing 2,024 patients, and found that IVI significantly increased Hb levels at various crucial time points: preoperative (MD=1.17, CI 95% [0.95, 1.40], P<0.01), postoperative day one (MD=1.32, CI 95% [0.89, 1.76], P<0.01), hospital discharge (MD=0.76, CI 95% [0.28, 1.24], P=0.002), and 30 days postoperative (MD=1.57, CI 95% [1.27, 1.87], P<0.01). The overall need for RBCT significantly decreased with IVI (RR=0.39, CI 95% [0.27, 0.56], P<0.01), particularly in the postoperative period (RR=0.69, CI 95% [0.52, 0.92], P=0.01). No significant differences were found between preoperative and intraoperative periods. IVI notably reduced transfused red blood cell units, total complications, and wound dehiscence. However, there were no significant differences in total death, hospital stay, OS and DFS.

Conclusion

Preoperative IVI significantly increased Hb levels at critical time points and markedly reduced the overall need for RBCT, complications, and wound dehiscence. To further validate these findings, more well-designed randomized controlled trials are warranted.

Introduction

Managing decompensated cirrhosis is a significant challenge due to high morbidity and mortality rates. The recently proposed Baveno VII criteria provide a standardized definition to assess recompensation. In this study, we validated the Baveno VII definition of recompensation and aimed to evaluate recompensation factors in patients with decompensated viral cirrhosis.

Aims & Methods

This is a retrospective descriptive study over a 10-year period between 2012 and 2022, enrolling 99 patients from the hepato-gastroenterology department of Mohamed Taher Maamouri Hospital in Nabeul who had been treated for decompensated viral cirrhosis B or C and achieved sustained virological response with a follow-up of at least 12 months.

Results

A total of 99 patients with decompensated viral cirrhosis (B or C), who had received treatment and achieved sustained virological response, were included in the study. The mean age was 62 ± 11 years, and 56 patients were female. The most common mode of decompensation was ascites, observed in 81.8% of the patients. The mean MELD score was 15 ± 4, and the majority (59.7%) were classified as Child-Pugh class B. Overall, 45.5% of the decompensated patients achieved recompensation during the study period. The recompensation rate was higher in patients with hepatitis B-related cirrhosis (51.1%) compared to those with hepatitis C-related cirrhosis (40.4%).
According to the results of logistic regression, four independent factors associated with recompensation were found: albumin ( OR = 2.033, IC95% [1,461-2,827], p<0.001 ), diabetes ( OR =0.003, IC95%[0.000-0.045], p<0.001 ), Child Pugh score ( OR=0.162, IC95% [0.057-0.459], p=0.001 ), INR ( OR =0.017, IC95%[0.000-0.939].

Conclusion

This study identified key factors associated with recompensation in patients with viral decompensated cirrhosis, including serum albumin levels, INR values, history of diabetes, and severity of liver disease. The knowledge of recompensated indicators may help support the development of different prevention strategies to reduce the incidence of acute decompensation.

Introduction

With the advent of EUS guided biliary interventions, there is a lot of hype created that ERCP will cease to be performed. The most important and limiting factor for ERCP is successful bile duct cannulation. We have studied a large series of our cases and tried to study the impact of properly performed precut on success of bile duct cannulation.

Aims & Methods

Aim: To analyze the efficacy of freehand precut for selective cannulation in difficult ERCP and its role in improving technical success rate, obviating need for EUS guided / other rendezvous techniques.
Methods: Retrospective analysis of 3000 patients undergoing ERCP from 2017 till date for varied etiologies. No. of patients required precut accessotomy were noted and technical success rate was measured.

Results

No. of patients analyzed- 3000. Selective biliary cannulation- 2452 (81.74%). Difficult cannulations requiring freehand precut accessotomy- 548 (18.26%). Technical success after precut achieving biliary access- 539 (98.36%). Failure of biliary cannulation even after precut- 09 (1.64%). Most common etiology in precut casesstone disease 360 (65.70%) followed by malignant lesions 118 (21.53%), benign strictures 28 (5.11%), post cholecystectomy biliary leak 28 (5.11%), post traumatic biliary leak 10 (1.82%), post hydatid surgery biliary leak 02 (0.36%), post central hepatectomy biliary leak 02 (0.36%). Most common cause for failure in precut cases was extensive edema and deformed anatomy. Of all failed cases 3 were large stones who were subjected to surgery and 6 were malignant lesions who were subjected to EUS guided biliary drainage.

Conclusion

Free hand precut technique, done correctly, is a savior in difficult cannulation cases and it increases the success rate of selective biliary cannulation significantly avoiding the need for other costlier techniques such as EUS guided / Rendezvous techniques.

References

Mariani A, Di Leo M, Giardullo N, Giussani A, Marini M, Buffoli F, Cipolletta L, Radaelli F, Ravelli P, Lombardi G, D'Onofrio V, Macchiarelli R,
Iiritano E, Le Grazie M, Pantaleo G, Testoni PA. Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial. Endoscopy. 2016 Jun;48(6):530-5. doi: 10.1055/s-0042-102250. Epub 2016 Mar 18. PMID: 26990509.
Davee T, Garcia JA, Baron TH. Precut sphincterotomy for selective biliary duct cannulation during endoscopic retrograde cholangiopancreatography. Ann Gastroenterol. 2012;25(4):291-302. ​PMID: 24714256; PMCID: PMC3959408.

Introduction

Acute pancreatitis (AP) often has unpredictable and complicated clinical course. Numerous biochemical predictors may aid in the risk stratification of AP (including interleukin 6 (IL-6)), but none of them are accurate. YKL-40 is glycoprotein playing mayor role in inflammation and angiogenesis, with reported average serum concentrations of ≥ 190 ng/mL in inflammatory diseases. It has been shown that IL-6 stimulates the production of YKL-40 and, in reverse, YKL-40 (at least in some tissues) induces the production of IL-6.

Aims & Methods

The aim of our study is to assess whether combined concentrations of both YKL-40 and IL-6 could be more informative in risk stratification of developing more severe form of AP than concentrations of either biomarker alone.
We included 150 consecutive consenting adults with AP admitted to Sestre milosrdnice UHC, Zagreb (June 2020-June 2023). Patients with any acute/chronic diseases known to be associated with dysregulated expression of YKL-40 were excluded. Alongside routine laboratory studies (including C-reactive protein (CRP)), 7 mLs of blood were withdrawn for determining YKL-40 and IL-6 concentrations on admission and 48h after. Severity of disease was defined using revised Atlanta classification. Blood samples for YKL-40 and IL-6 quantification in 30 consenting non-AP adults consistent with previously mentioned exclusion criteria were withdrawn. They were matched 1:1 by age and sex to randomly selected 10 patients from each of AP severity categories. Analysis were performed using enzyme-linked immunosorbent assays. AP patients were classified into 2 categories for each biomarker (based on YKL-40 and IL-6 concentrations on admission and 48h after): 1. for YKL-40: low (<190 ng/mL) and high (≥190 ng/mL); 2. for IL-6: low (<42 pg/mL) and high (≥42 pg/mL). Cumulative multimodal logit models were fitted to ordinal outcome “AP severity” – using raw data, and data after entropy balancing undertaken to balance the two categories of YKL-40 and IL-6 concentrations on age, sex, time between symptom onset and admission, and CRP concentrations.

Results

The results showed lower YKL-40 (<50 ng/mL) and IL-6 (<20 pg/mL) concentrations in 30 non-AP adults compared to AP patients. At both time points (on admission and 48h after), odds of more severe AP were clearly higher with YKL-40 and IL-6 concentrations above vs. below the cut-off values (190 ng/mL and 42 pg/mL, respectively), and were particulary higher in patients with both cytokines above the cut-off vs. patients with both cytokines below the cut-off. The same relationship was maintained with adjustments for age, body mass index, days elapsed since symptom onset and admission, and for CRP concentrations – however, the strength of association was lower. This is in line with the fact that high CRP concentration predicts more strongly severe AP forms when taken 48h after compared to admission. This phenomenon was apparent also when the interaction term was included in the model: at CRP concentrations 45 mg/L, neither YKL-40, or IL-6 or their combination above the cut-off values were associated with the outcome; at CRP concentrations 90 mg/L, odds were higher, and were particularly high for a combination of high YKL-40 and high IL-6. The same was observed at CRP concentrations 180 mg/L.

Conclusion

Overall, data suggest that combined YKL-40 and IL-6 concentrations in acute AP, taken either on admission or 48h after, predict more strongly moderate and/or severe (vs. mild) AP than either cytokine alone, and do so 'on-top' of the CRP concentrations.

References

1. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG et al. Classification of acute pancreatitis - 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–111.
2. van den Berg FF, de Bruijn AC, van Santvoort HC, Issa Y, Boermeester MA. Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis. Pancreatology. 2020;20(7):1302-1311.
3. Tizaoui K, Yang JW, Lee KH, Kim JH, Kim M, Yoon S et al. The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review. Int J Biol Sci. 2022;18(9):3731-3746. doi: 10.7150/ijbs.67587.
4. Blazevic N, Rogic D, Pelajic S, Miler M, Glavcic G, Ratkajec V et al. YKL-40 as a biomarker in various inflammatory diseases: A review. Biochem Med. 2023;34(1):010502.

Introduction

Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer in eastern Asia and Africa. Diagnosis at early stage is crucial to reduce the mortality of ESCC. Currently, esophagogastroduodenoscopy (EGD) is the golden standard for screening ESCC, however, the patient compliance rate has been low due to the invasiveness and high cost of EGD. Thus, there is an unmet need for the development of diagnostic modality that enables non-invasive early detection of ESCC.

Aims & Methods

The purpose of this study is to construct a urinary exosomal miRNA panel as a least invasive test that can detect ESCC with high accuracy and validate its performance in a prospective cohort enriched with early ESCC. We prospectively collected urine samples from 161 ESCC patients and 180 healthy controls (HC) at five institutions from September 2019 to March 2023. Exosomes were extracted from urine specimens by polymer precipitation method, and exosomal miRNAs were subjected for comprehensive expression analysis by small RNA seq. Of the 341 total samples, 309 samples (90.6%) that passed the QC check were selected for subsequent data-analysis. In the training cohort (100 samples of ESCC and 98 samples of HC), we measured the expression of 328 miRNAs to identify candidate biomarker miRNAs. A miRNA diagnostic panel was constructed using machine learning analysis, and diagnostic performance was evaluated using a 5-fold cross-validation method. In the validation cohort (50 samples of ESCC and 61 samples of HC), the diagnostic performance of the urinary miRNA diagnostic panel was verified with blind to clinical information.

Results

In the RNAseq analysis of the training cohort (ESCC; mean age 68.2 years, 77.9% male; HC; mean age 58.1 years, 76.3% male), 33 out of 328 miRNAs were differentially expressed between ESCC and HC. Out of the 33 dysregulated miRNAs, 21 were upregulated and 12 were down-regulated. A multi-miRNA biomarker panel composed of miRNAs that were individually significant and non-significant between ESCC and HC had a diagnostic performance of AUC 0.89 (95% CI 0.84 to 0.94) by 5-fold cross-validation. In the validation cohort (ESCC; mean age 63.0 years, 78.0% male, median size 32mm, Stage I/II/III/IV 54/10/26/10%, HC; mean age 51.0 years, 52.5% male), The diagnostic performance of the miRNA diagnostic panel was AUC 0.85(95% CI 0.80 to 0.90), with a sensitivity of 84%, specificity of 73.8%, and accuracy of 78.4% at a pre-defined cutoff value. There was no confounding of diagnostic performance by age, gender, BMI, history of alcohol consumption or smoking. The sensitivity by clinical stage of ESCC was 88.9/80.0/77.8/80% for Stage I/II/III/IV.

Conclusion

We developed and validated a urinary exosomal miRNA diagnostic panel, which may be a new non-invasive diagnostic method that contributes to the early detection of ESCC.

Disclosure

Tomonori Yano received research funding from Craif Inc.

Introduction

Colorectal cancer, with an estimated two million new cases each year worldwide, poses a significant socioeconomic burden on modern society. It is the second leading cause of cancer-related deaths, accounting for nearly one million premature deaths annually.

Aims & Methods

The role of Signal Transducer and Activator of Transcription 2 (STAT2) in this context is not yet understood, and no therapies targeting this transcription factor are currently being pursued. We explored the function of STAT2 in colorectal cancer by employing experimental mouse models, as well as conducting functional assays with three-dimensional tumoroids in the context of anticancer therapy.

Results

In vivo studies showed that Stat2KO mice were more resistant to developing tumors in both inflammation-driven and inflammation-independent models of experimental colorectal cancer. This unexpected outcome could not be reconciled with the known role of STAT2 in inducing cell death downstream of type I interferon signaling. We consequently performed ex vivo experiments with tumoroids derived from Stat2KO mice carrying the multiple intestinal neoplasia (Min) mutant allele of the adenomatous polyposis coli (Apc) gene. These tumoroids exhibited slower growth, were generally smaller in size, and showed a higher degree of differentiation compared to those derived from ApcMin/+ wildtype mice. Remarkably, when treated with anti-tumor agents that induce cell death through various mechanisms, tumoroids derived from ApcMin/+ Stat2KO mice were found to be highly sensitive. Additional functional studies indicated that the underlying mechanism might involve a STAT2-dependent disruption of innate immune DNA sensing.

Conclusion

Our results establish STAT2 as a promoter of colorectal cancer and a contributor to resistance against anti-tumor therapy. These findings suggest that targeting STAT2-dependent signaling could be a promising therapeutic strategy for patients with colorectal cancer.

Introduction

Irritable bowel syndrome (IBS) is a highly prevalent and challenging condition with limited therapeutic options. Chitin-glucan (CG) is a novel dietary prebiotic considered as a safe food ingredient by EFSA. To provide an alternative approach to the management of IBS patients, we evaluated in preclinical studies the roles of CG on visceral analgesia, intestinal inflammation and barrier function and performed an open-label trial in IBS patients.

Aims & Methods

Analgesic effect of CG used at a human equivalent dose (HED) of 1.5-3 g/d was evaluated in rats and compared to negative-tap water and positive-phloroglucinol control groups. Mice with DSS-induced colitis were used to analyze the anti-inflammatory properties of CG. Molecular mechanisms underlying analgesic, anti-inflammatory, and intestinal barrier-strengthening functions of CG were evaluated in human intestinal HT-29 epithelial cells. CG molecular modeling was developed to study its interactions with microbial cell walls.
A multicenter open-label trial was conducted in 120 patients with IBS (Rome IV criteria) treated with CG 1.5 g/d and simethicone 0.75 mg/d for 4 weeks. The primary endpoint was the responder rate, defined as the number of patients whose abdominal pain score decreased by ≥30% from baseline at week (W) 4. The analysis was performed using the per-protocol set. Cardinal symptoms, impact of global symptoms on daily life, change in stool consistency, and improvement in defecatory disorders were evaluated.

Results

CG in animals was well tolerated. CG at 3g/d HED significantly decreased visceral perception by 14% after 2 weeks (p<0.01) and reduced inflammation by 50% promoting mucosal regeneration in DSS-induced colitis mice. CG at 1.5g/d HED reduced visceral pain perception by 20% after 5 weeks of treatment (p<0.01). At 3g/d HED, this analgesic effect was superior to phloroglucinol with a faster onset of action and a 50% inhibition of pain perception (p<0.0001). The molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved a significant induction of µ-opioid receptor (MOR), cannabinoid-2 (CB2) receptor, IL-10 and a significant decrease of pro-inflammatory cytokines IL-1b and IL-8 mRNA. CG also significantly up-regulated barrier-related genes like muc5AC, claudin-2 and ZO-2. CG molecular modelling revealed a new property of the molecule as a chelator of gram–negative lipopolysaccharide (LPS), gram–positive lipoteichoic acid (LTA) and phospholipomannan (PLM) in fungi.
Overall, 100 IBS patients were evaluated. At week 4, 67% were abdominal pain responders (score: 5.8 ± 2.4 vs. 2.9 ± 2.0, p<0.0001). Similar improvements were observed for bloating (8.0 ± 1.7 vs. 4.7 ± 2.9, p<0.0001; 60% responders), abdominal distension (7.2 ± 2.1 vs. 4.4 ± 3.1, p<0.0001; 53% responders), and impact of global symptoms on daily life (7.1 ± 2.0 vs. 4.6 ± 2.9, p<0.0001; 54% responders). Stool consistency improved in most patients (90% and 57% for patients with liquid and hard stools, respectively). Overall, 42% of patients with defecatory disorders reported very much/considerable improvements by 2 weeks. No severe adverse event occurred, and tolerability was rated “good” or “very good” by 93%.

Conclusion

CG decreased visceral perception and intestinal inflammation. It also impacted master genes regulation and direct binding of microbial products. CG-simethicone was well tolerated and improved IBS symptoms in an uncontrolled trial. A placebo-controlled trial with longer follow-up is now ongoing to confirm the benefits of CG in IBS patients.

Disclosure

Prof Pierre Desreumaux is President of the Scientific Board of BiOkuris SA
Prof Edouard Louis is member of the Scientific Board of BiOkuris SA