Introduction

The degree of fibrosis during colorectal ESD varies and sometimes makes the procedure itself difficult. Preoperative prediction of fibrosis is expected to help develop a reliable strategy.

Aims & Methods

Of 1309 colorectal ESD lesions performed at our hospital between April 2012 and September 2022, 953 lesions larger than 20 mm were included after excluding post-treatment recurrence, SMT, and other conditions. Intraoperative fibrosis was classified into F0 (none), F1 (mild), and F2 (severe).

Results

Fibrosis was observed in 192 (20.1%) patients (F1; 143, F2; 49). The tumor diameter (median, range) was 23 (20-135), 30 (20-210), and 35 (20-115) mm in F0, F1, and F2 groups, respectively. The rate of the cecum (%) was 13.3 : 29.4 : 16.3, which was higher in F1. Overall, bleeding was observed in 17 patients (1.8%) and perforation in 3 patients (0.3%), and the frequency was similar in each group. The curative resection rate (%) was 98.4:91.6:59.2, with F2 being significantly inferior. The long treatment time (≥120 minutes) (%) was 1.7 : 9.1 : 46.9, showing a significant difference between F0 vs F1 and F1 vs F2, and the dissection speed (mean±SD, mm²/min) was 25.9±14.5 : 23.2±13.6 : 15.3±10.6, which was significantly slower in F2. The predictive factors of F1 and F2: straddling the folds, prior biopsy, lesion diameter, site, and morphology, were included in the study, and multivariate analysis showed that the predictive factors of F1 were straddling folds (OR;2.07,95%CI;1.39-3.11), lesion diameter ≥50mm (OR;4.68,95%CI;2.45-8.94), biopsy (OR;6.44,95%CI;3.32-12.5), NGPD (OR;4.31,95%CI;2.37-7.83), and cecum(OR;3.73,95%CI;2.35-5.92). The predictive factors of F2 were straddling folds (OR;2.34,95%CI;1.21-4.51), lesion diameter ≥50 mm (OR;7.29,95%CI;3.03-17.5), biopsy (OR;5.07,95%CI;1.81-14.1), and protruded type (OR;6.44,95%CI;3.23-12.8).

Conclusion

Colorectal ESD for fibrotic lesions was safe, but the curative resection rate was low in F2. F1-specific predictors were cecum and NGPD, and F2-specific predictors were protruded type, suggesting that the choice of surgeon and strategy should depend on the expected degree of fibrosis.

Introduction

Autoimmune Atrophic Gastritis (AAG) is a chronic immune-mediated condition that mainly affects the body and fundus of the stomach. AAG is often under-diagnosed due to the slow progression of the disease and a variable spectrum of symptoms. Recent data suggests a potential role of altered gastric microbiota in the natural history of AAG, due to the potential overgrowth of bacteria linked to the development of neoplastic complications (neuroendocrine tumors- NETs and gastric cancer) (1,2). Moreover, the same data hypothesizes the use of fecal microbiota as a possible non-invasive marker to diagnose and monitor AAG. Thus, we aimed to prospectively characterize the salivary and fecal microbiota of patients with AAG to provide further insights in this field.

Aims & Methods

We collected salivary and fecal samples from consecutive patients with an established diagnosis of AAG, enrolled at the Gastroenterology Unit of Azienda Ospedale Università Padova from March to June 2023 at the time of endoscopic follow-up examination. All patients needed to be off Proton-Pump Inhibitors, antibiotics, and probiotics for at least one month before enrolment. Stool samples were collected by the patients on the day of the endoscopy, transferred in a buffer solution, and stored at -20°C. Oral samples were collected through salivary commercial kits and freezed at -20°C. Both salivary and faecal samples were analyzed by BMR Genomic (Padua, Italy) that amplified the V3-V4 hypervariable ribosomal RNA region. Sequencing of the 16S rRNA gene V3- V4 region was performed using the Illumina MiSeq. Preliminary analyses were conducted on individual fecal samples compared to an internal population of healthy subjects (provided by BMR genomics) using Qiime2 tools. Shannon–Wiener index was used to calculate α-diversity and then the microbial biodiversity index (MBI) and Dysbiosis Index (DI). Mann–Whitney tests were performed to verify statistical differences in the α-diversity across AAG patients and healthy subjects.

Results

We enrolled 15 AAG patients with a mean age of ± 63 ± 11 years (9/15 females). OLGA 2 stage was reported in 10/15 patients. Sixty percent of the patients showed a MBI between 7.11 and 12.45, indicating that each sample contained phylogenetically similar species. The remaining patients have an index greater than 12.45 compared to the healthy population. More than half of the patients had dysbiosis (>0.082). The highest indices of dysbiosis were found in patients with a history of NET (n=3), gastric cancer (n=1), and previous HP- infection and OLGA 3 stage (n=1). Firmicutes, Bacteroidetes, and Proteobacteria were more frequent phyla found in the fecal samples, whereas Enterobacteriaceae and Streptococcaceae were the most common bacterial families (13/15, 87%). In particular, Klebsiella and Campylobacter pathogens genera were found in some samples. Streptococcus and Prevotella were the most abundant genera found in the salivary samples.

Conclusion

Patients with AAG were found to have a great proportion of Firmicutes and Bacteroidetes, which aligns with the literature (3,4). Moreover, a dominant of Proteobacteria, especially Enterobacteriaceae commonly associated with proinflammatory states, was found. (5) Our preliminary data showed a possible positive association between higher degrees of dysbiosis and a previous history of NET or gastric cancer.

References

1. Parsons BN, Ijaz UZ, D'Amore R, Burkitt MD, Eccles R, Lenzi L, Duckworth CA, Moore AR, Tiszlavicz L, Varro A, Hall N, Pritchard DM. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use. PLoS Pathog. 2017 Nov 2;13(11):e1006653.

2. Conti L, Annibale B, Lahner E. Autoimmune Gastritis and Gastric Microbiota. Microorganisms. 2020 Nov 19;8(11):1827.

3. Castaño-Rodríguez N, Goh KL, Fock KM, et al. Dysbiosis of the microbiome in gastric carcinogenesis. Sci Rep. 2017;7(1):15957.

4. Conti L, Borro M, Milani C, Simmaco M, Esposito G, Canali G, Pilozzi E, Ventura M, Annibale B, Lahner E. Gastric microbiota composition in patients with corpus atrophic gastritis. Dig Liver Dis. 2021 Dec;53(12):1580-1587.

5. Rizzatti G, Lopetuso LR, Gibiino G, Binda C, Gasbarrini A. Proteobacteria: A Common Factor in Human Diseases. Biomed Res Int. 2017;2017:9351507.

Disclosure

Nothing to disclose

Introduction

Advanced chronic liver disease (ACLD) may present in different stages with distinct prognoses. Child-Pugh and MELD scores are commonly used models for predicting liver-related mortality and decompensation, but they have several limitations. An alternative or complementary tool that is simple and cost-effective would be invaluable. Recently, some studies identified a potential role of ammonia in predicting liver-related outcomes.

Aims & Methods

Our primary objective was to explore the predictive role of plasma ammonia levels regarding liver-related complications and mortality. Our secondary aim was to validate a new measure that corrects baseline ammonia levels to the upper limit of normal (AMM-ULN) and test a cut-off which was proposed in the literature to define patients at higher risk of such outcomes (AMM-ULN ≥ 1.4).
This retrospective study included 278 patients with ACLD who had an ammonia measurement in our hospital between 2018 and 2022. ACLD patients were divided into compensated and decompensated stages, with the latter being subdivided into three stages, according to the type of decompensation. Outcomes of liver-related decompensation and mortality were assessed in each group. AMM-ULN was evaluated as a predictor of these outcomes both in compensated and decompensated patients. The predictive accuracy of AMM-ULN was then determined by identifying the best cut-off.

Results

Plasma ammonia levels and AMM-ULN were predictors of hepatic decompensation (HR = 1.453, 95%CI 1.085 – 1.945, p = 0.012) and mortality (HR = 1.010, 95%CI 1.003 – 1.017, p < 0.001) at 12 months, in the compensated patient group. The AUROC for AMM-ULN was 67.4% in 1-year decompensations and 69.5% in 1-year mortality, with similar results for ammonia levels. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months (p = 0.009 and p = 0.020, respectively).

Conclusion

Both ammonia levels and AMM-ULN were predictors of hepatic decompensation and liver-related mortality in compensated patients, at 12 months of follow-up. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months.

References

D’Amico, G., Garcia-Tsao, G., & Pagliaro, L. (2006). Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. Journal of Hepatology, 44(1), 217–231. https://doi.org/10.1016/j.jhep.2005.10.013
Haj, M., & Rockey, D. C. (2018). Predictors of clinical outcomes in cirrhosis patients. Current Opinion in Gastroenterology, 34(4), 266–271. https://doi.org/10.1097/MOG.0000000000000450
De Franchis, R. et al (2022). Baveno VII – Renewing consensus in portal hypertension. Journal of Hepatology, 76(4), 959–974. https://doi.org/10.1016/j.jhep.2021.12.022
Shalimar, Sheikh, M. F. et al (2019). Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology, 70(3), 982–994. https://doi.org/10.1002/hep.30534
Tranah, T. H. et al (2022). Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis. Journal of Hepatology, 77(6), 1554–1563. https://doi.org/10.1016/j.jhep.2022.07.014
Balcar, L. et al (2023). Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease. JHEP Reports, 5(4), 100682. https://doi.org/10.1016/j.jhepr.2023.100682
Elzeftawy, A. et al (2018). Evaluation of the blood ammonia level as a non-invasive predictor for the presence of esophageal varices and the risk of bleeding. The Turkish Journal of Gastroenterology. https://doi.org/10.5152/tjg.2018.17894

Introduction

The randomized controlled OPTIC trial reported that optimised mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at one year in ulcerative colitis (UC) patients failing 5-aminosalicylates after receiving induction treatment with corticosteroids.

Aims & Methods

We aimed to assess cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment in UC. Data were collected during the OPTIC trial to perform a health economic evaluation for mercaptopurine treatment versus placebo in UC patients. The economic evaluation was performed from a health care and societal perspective using a cost-effectiveness and cost-utility analysis with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. Main outcomes were the costs per patient who achieved combined corticosteroid-free clinical remission and endoscopic improvement at one year and the costs per quality-adjusted life-year (QALY).

Results

In total, 59 patients were randomized to the intervention (n = 29) and control (n = 30) group. Patients on mercaptopurine treatment showed a non-significant gain in QALYs of 0.047 (-0.024 to 0.117) (P=0.184) corrected for baseline health utility. Non-significant differences in costs were €63 (-€1267 to €1434; P=0.927) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P=0.644) in favour of mercaptopurine from a societal perspective, including patients’ out-of-pocket expenses and employers’ productivity loss. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000.

Conclusion

Optimised mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.

References

1. de Boer NKH, Peyrin-Biroulet L, Jharap B, et al. Thiopurines in inflammatory bowel disease: new findings and perspectives. J Crohns Colitis 2018;12:610–20.
2. Löwenberg, M., Volkers, A., van Gennep, S., Mookhoek, A., Montazeri, N., Clasquin, E., Duijvestein, M., van Bodegraven, A., Rietdijk, S., Jansen, J., van Asseldonk, D., van der Zanden, E., Dijkgraaf, M., West, R., de Boer, N., & D'Haens, G. (2023). Mercaptopurine for the Treatment of Ulcerative Colitis: A Randomized Placebo-Controlled Trial. Journal of Crohn's & Colitis, 17(7), 1055–1065.

Disclosure

NA

Introduction

Filgotinib is a selective JAK1 inhibitor recently licensed for use in moderate-severe Ulcerative Colitis (UC)​¹​​​​.

Aims & Methods

We sought to review outcomes for patients commenced on Filgotinib for UC in the Glasgow South Sector IBD Service. Patients were identified using the local IBD Biologics Database. Electronic patient records were reviewed for demographics, previous treatment, and outcomes since commencing Filgotinib.

Results

28 patients were commenced on filgotinib between July 2022 and February 2023. 21.4% were female and 78.6% male with a median age of 38y. By Montreal classification, 3.6% were classified as E1, 64.3% as E2 and 32.1% as E3. 50% of patients were biologic naïve with 71.4% on concomitant treatment with aminosalicylate. Median follow-up was 4 months.
78.6% (22/28) reported improvement in their symptoms with only 21.4% (6/28) experiencing side effects (SEs). 64.3% in the biologic-naïve group found subjective improvement in symptoms with 85.7% noting improvement in the biologic-experienced group. SEs included infections (3), Increase in cholesterol/triglycerides (2) and subjective worsening of low mood (1).
17 Patients had pre and post-treatment Faecal calprotectin (FC) available. Of those patients, 70.6% had an improvement with an overall reduction in median FC level from 1567 to 203 across the group. This reduction did not reach statistical significance.
7/28 patients required a course of rescue steroids after starting treatment. No patients required IP admission since commencing treatment. 5/28 were considered to have a primary non-response to Filgotinib. Of these, 4 were switched to alternative advanced therapies and 1 awaits surgery.

Conclusion

Filgotinib appears a safe and effective treatment in moderate-severe UC for both biologic-naïve and experienced patients. Its oral route of administration and quick onset mechanism of action make it an appealing choice. Further real-world data is required with larger patient cohorts to establish its true utility in routine clinical practice.

References

1. D’Amico, F. et al. (2021) “Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis,” Journal of Crohn’s and Colitis, 16(5), pp. 835–844. Available at: https://doi.org/10.1093/ecco-jcc/jjab206.

Introduction

Biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is a common palliative endoscopic procedure for unresectable malignant biliary obstruction or for patients unfit for surgery.

Aims & Methods

We conducted a multicentre retrospective cohort study in 3 centres in Portugal, involving patients submitted to first palliative biliary drainage for malignant biliary obstruction by ERCP, between 2015 and 2022. This study aimed to identify predictive factors of 90-day mortality after endobiliary drainage and propose a predictive model. We have analysed data from 217 patients. Statistical analysis was performed using SPSS v.29.

Results

In our cohort, 51,2% (N=111) of patients were female and the mean age was 74 years. 52,5% (N=114) had stage IV disease and in 88% (N=191) the biliary obstruction resulted from primary tumour involvement. The most frequent tumour was primary pancreatic cancer (53,5%, N=116), followed by cholangiocarcinoma (26,7%, N=58). Metallic stents were used in 53,9% (N=117) of the patients, mainly with fully uncovered self-expandable metallic stents (66,7%, N=78). In the multivariate regression model, the independent predictors for 90-day mortality after first ERCP-guided stent placement were primary tumour size <3 cm (p = 0,014; OR 0,394; 95% CI, 0,187-0,830), stage IV malignant disease (p = 0,005; OR 3,776; 95% CI, 1,507-9,465), intrahepatic biliary obstruction (p = 0,004; OR 3,727; 95% CI, 1,518-9,150) and palliative chemotherapy after ERCP biliary drainage (p <0,0001; OR 0,44; 95% CI, 0,015-0,132). Using these variables, we developed a prediction model for the risk of mortality within 90 days after biliary drainage (Hosmer-Lemeshow X² = 2,907, p = 0,893) with R² of 44,1% in our cohort. The AUROC for our prediction model was 0,833 (p <0,0001; 95% CI, 0,774-0,892). By the Youden’s J statistic, the optimal cut-off value for was 0,4, with a sensitivity of 73,9% and specificity of 76,3%. Patients with a score < 0,2 had a low likelihood of death, whereas a score ≥ 0,9 had a high likelihood of death.

Conclusion

The present study was able to identify statistically significant predictive factors of 90-day mortality after ERCP-guided biliary stenting in unresectable malignant biliary obstruction, which may help to stratify the risk of death within 90 days post-stent placement. Since all these predictive factors can be determined before ERCP, this risk stratification could help in the definition of the proper palliative strategy for each patient.

References

Termsinsuk, P., Charatcharoenwitthaya, P., & Pausawasdi, N. (2022). Development and validation of a 90-day mortality prediction model following endobiliary drainage in patients with unresectable malignant biliary obstruction. Frontiers in oncology, 12, 922386. https://doi.org/10.3389/fonc.2022.922386;
Sripongpun, P., Attasaranya, S., Chamroonkul, N., Sookpaisal, T., Khow-Ean, U., Siripun, A., Kongkamol, C., Piratvisuth, T., & Ovartlarnporn, B. (2018). Simple Clinical Score to Predict 24-Week Survival Times in Patients with Inoperable Malignant Distal Biliary Obstruction as a Tool for Selecting Palliative Metallic or Plastic Stents. Journal of gastrointestinal cancer, 49(2), 138–143. https://doi.org/10.1007/s12029-017-9918-9;
Afshar, M., Khanom, K., Ma, Y. T., & Punia, P. (2014). Biliary stenting in advanced malignancy: an analysis of predictive factors for survival. Cancer management and research, 6, 475–479. https://doi.org/10.2147/CMAR.S71111.

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]