Introduction

ESD is an excellent endoscopic treatment with high en-bloc and R0 resection rate. However, duodenal ESD is technically difficult. And, it has been reported that the perforation rate of duodenal ESD is higher than that of ESD of other organs.
Hybrid ESD, which involves circumferential incision followed by removal of the lesion using a snare, may shorten the operation time, but detailed studies have not been conducted.

Aims & Methods

The aim of this study was to compare the treatment outcomes of ESD and hybrid ESD for duodenal tumors.
The subjects were superficial duodenal tumors that were resected at Saku Central Hospital from Dec.2002 to Dec. 2023, and diagnosed as grade 3 or 4 according to the Vienna classification.
ESD and Hybrid ESD were performed for 16 and 148 patients. Gender (Male/Female), age and location (1^st, 2^nd, 3^rd) of both groups were 18/8, 106/42, 64 (39-84), 62 (37-84) and (4/18/4), 9/119/20, respectively. There was no significant difference.

Results

1. Paris classification 0-I/IIa/IIb/IIc were 2/17/1/6 and 3/6/0/84, respectively.
2. En-bloc resection rate was 100% (26/26) and 89% (131/148), respectively (p=0.07). R0 resection rate was 100% (26/26) and 82% (121/148), respectively (p=0.01).
3. Size of tumor and specimen were 20 (5-63) / 9(2-27) and 28 (17-66) / 16 (8-34) mm, respectively (P<0.001、P<0.001).
4. Duration of procedure was 95 (34-265) and 30 (8-34), respectively (P<0.001).
5. Complications: Perforation, delayed perforation and delayed bleeding were 0% and 2.7% (4/148), 3.8% (1/26) and 2% (3/148), 0% and 0.7% (1/148), respectively. There was no significant difference.
6. Local recurrence rate was 0%, 0.7% (1/148), and the only local recurrent case was treated by HOT biopsy.
Hybrid ESD was useful for shortening treatment duration, however the R0 rate were significantly lower. Recently, under water EMR has been applied to the duodenal lesions, and it seems necessary to conduct a comparative study of hybrid ESD and under water EMR in the future.

Conclusion

ESD has excellent R0 resection rate, however it is technically difficult and has long treatment duration. On the other hand, hybrid ESD shortens treatment times but has lower R0 resection rates. Therefore, the indication of hybrid ESD is limited. Further examination including under water EMR should be performed.

References

None

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

In the early phase of acute pancreatitis (AP), fluid resuscitation plays a crucial role. Changes in fluid distribution, increased capillary permeability, minimized intravascular volume, and loss of vascular resistance may lead to cardio-vascular and renal failure. On the other hand, overhydration is associated with cardiac decompensation and respiratory failure. Previously, intensive fluid therapy with large volumes of crystalloids was recommended without addressing individual needs for fluid therapy.
We used measurements of physiological parameters focusing on cardiac function and changes in body composition, to study the association between fluid therapy and physiological response, in the patient with AP.

Aims & Methods

This study aimed to assess fluid distribution in relation to fluid therapy, inflammation, and cardiac- and renal function in the early phase of AP.
This was a single-centre, prospective observational cohort study. On baseline, day 1, 2, 10 and 90 following were assessed: preload dependency (passive leg raise manoeuvre and defined as a >10% increase in stroke volume), hemodynamic parameters (stroke volume, cardiac output measured by non-invasive monitoring (Non-invasive LiDCOrapidTM; LiDCO, London, UK)), bioimpedance variables (weight, extracellular water (ECW), total body water(TBW) by seca mBCA 525, Germany). White blood count (WBC), C-reactive protein (CRP), and creatinine were measured and Modified Marshall score was calculated on each time point. Data are presented as medians with interquartil range (IQR). [jK1] Pearson correlation coefficient was used to assess the relationship between changes in weight and haemodynamic and bioimpedance parameters.

Results

Eighty-eight patients with first-time AP were included. Median age was 58 years, 46 were females. Gallstones were the predominant etiology (55%). At baseline, 35 patients (40%) were preload dependent. However, the median increase in weight during the first 10 days of admission was 2.65 kg (IQR: 0.9;4.73). Across time points, patients in the fourth upper quartile of weight increase had significantly higher volume of ECW than patients in the 1-3. quartile (p=0.02). No differences were observed for stroke volume, nor cardiac output. CRP was significantly higher in patients in the fourth upper quartile of weight increase than in patients in quartile 1-3. No difference was found for WBC and creatinine.
We found a significant correlation between increasing bodyweight and extracellular water volume, R=0.383, (p<0.0001), but not between increasing bodyweight and stroke volume R=-0.016 (p=0.783) or cardiac output, R=0.015 (p=0.796). Also, a significant correlation was found between creatinine and increasing weight, R=0.229 (p<0.0001). Modified Marshall score was significantly correlated to increasing body weight, R=0.159 (p=0.006).

Conclusion

The assessment of hydration status in AP requires an in-depth knowledge of body fluid homeostasis. Our data provide physiological rationale for emerging evidence regarding more restricitive fluid resuscitation. Personalized- and goal directed therapy may be a promising novel way in the transition from necessary fluid resuscitation to harmful fluid volume accumulation in the early phase of AP.

References

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications.
Dumnicka P, Maduzia D, Ceranowicz P, Olszanecki R, Drożdż R, Kuśnierz-Cabala B.
Int J Mol Sci. 2017 Feb 8;18(2):354. doi: 10.3390/ijms18020354.
Tenner S, Baillie J, DeWitt J, Vege SS;
American college of Gastroenterology guideline: management of acute pancreatitits
Am J Gastroenterol 2013; 108: 1400-16.27.
Working group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidencebased guidelines for the management of acute pancreatitis
Pancreatology 2013; 13:Suppl 2:e1-e15
Disturbances of the microcirculation in acute pancreatitis.
Cuthbertson CM, Christophi C.
Br J Surg. 2006 May;93(5):518-30. doi: 10.1002/bjs.5316.
Fluid Resuscitation in Acute Pancreatitis - Going over the WATERFALL.
Gardner TB
N Engl J Med. 2022 Sep 15;387(11):1038-1039. doi: 10.1056/NEJMe2209132.

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.