Introduction

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is reported to be useful as an alternative treatment for patients who are unable to undergo transpapillary bile duct drainage. EUS-hepaticogastrostomy (HGS), which involves a transgastric approach to the left intrahepatic bile duct, has been suggested as the first-line approach for EUS-BD because of a lower risk of bile leakage in patients with dilated intrahepatic bile ducts. However, there are few reports comparing the effectiveness and safety of EUS-BD procedures between EUS-HGS and EUS-HGS with antegrade stenting (EUS-AS+HGS).

Aims & Methods

Therefore, we compared the efficacy and safety of EUS-AS+HGS and EUS-HGS as drainage methods in EUS-BD. From April 2017 to December 2020, we retrospectively evaluated patients who underwent EUS-AS+HGS or EUS-HGS in our hospital for unresectable malignant biliary obstruction for which transpapillary biliary drainage had failed. We compared the time to recurrence of biliary obstruction (TRBO), overall survival, technical success rate, clinical success rate, adverse event rate, reintervention rate, and length of hospital stay between each procedure.

Results

A total of 68 patients, 22 in the EUS-AS+HGS group and 46 in the EUS-HGS group, were included in the study. In the EUS-HGS group, 38 patients underwent HGS only, while EUS-AS+HGS was attempted in another 8 patients who ultimately underwent EUS-HGS because of unsuccessful guidewire penetration. In the EUS-AS+HGS group, the TRBO was significantly longer, and the re-intervention rate significantly lower than in the EUS-HGS group (both p=0.03). However, there were no significant differences in technical success rate, overall survival, clinical success rate, adverse event rate, and length of hospital stay.

Conclusion

EUS-AS+HGS was superior to EUS-HGS regarding the length of biliary patency and re-intervention rate in patients with unresectable malignant biliary obstruction. The results suggest that EUS-AS+HGS is the preferred treatment when guidewire penetration of the biliary stricture is possible.

Introduction

Acute severe colitis (ASC) is an important cause of morbidity and mortality in Ulcerative Colitis (UC), requiring hospitalisation and, frequently, colectomy. Intravenous corticosteroids (CS) remain the first-line medical treatment. Approximately 40% of episodes of ASC do not respond to this treatment and require rescue therapy with ciclosporin (CIC) or infliximab (IFX)¹. In the past decades, these treatments and protocol-driven management algorithms led to reduced mortality and colectomy rates. A simple clinical scoring system (the Admission Model for the Intensification of Therapy in Acute Severe Colitis (ADMIT-ASC))³, based on CRP, albumin, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, was recently developed to predict the steroid response on admission.

Aims & Methods

We aimed to retrospectively assess the steroid non-response during admission with ASC and the usefulness of the new prognostic clinical index ADMIT-ASC at admission to predict steroid response in a Belgian tertiary center. All patients admitted with ASC between 1^st January 2015 and 1^st April 2023 were identified from our inflammatory bowel disease database at Erasme University Hospital. Inclusion criteria were ASC patients admitted at the hospital, standard treatment with at least 3 days of intravenous CS and endoscopy evaluation upon admission. ASC was defined according to modified Truelove and Witts’ criteria as ≥6 bloody stools/day with one or more markers of systemic disturbance (tachycardia >90 beats/min, temperature >37.8°C, haemoglobin <105 g/L or CRP >30 mg/L). Steroid non-response was defined as the need for medical rescue therapy (CIC of IFX) or colectomy during the admission. ADMIT-ASC index consists of four points: CRP ≥100 mg/L (1 point), albumin ≤25 g/L (1 point) and UCEIS score ≥4 (1 point) or ≥7 (2 points).

Results

Table I Admission Demographics data (n= 84)	Steroid response (n=49)	Steroid non-response (n=35)	P value
Median disease duration (years) (IQR)	3.6 (0.3-0.9)	2.1 (0.8-5.5)	0.5
Montreal Classification	E1 : 5/49 (10%) E2 : 20/49 (41%) E3 : 24/49 (49%)	E1 : 0/35 E2 : 12/35 (34%) E3 : 23/35 (66%)	0.084
5-ASA, n (%)	22 (45%)	10 (29%)	0.13
Methotrexate or thiopurine, n (%)	6 (12%)	9 (26%)	0.11
Infliximab, n (%)	4 (8.2%)	8 (23%)	0.058
Vedolizumab, n (%)	7 (14%)	5 (14%)	>0.9
Tofacitinib, n (%)	2 (4.1%)	2 (5.7%)	>0.9
Readmission, n (%)	12 (24%)	10 (29%)	0.7
5-ASA, 5-aminosalicylate P values from Wilcoxon rank-sum test or Fisher’s exact test.

Out of 127 patients admitted with UC and treated with intravenous CS during three days, 84 (45% male, median age of 31 years old) were included in the study. Admission demographics and clinical characteristics are described in Table 1.
For 17 patients (20%), the admission was their index presentation of UC. Response to CS was seen in 49 patients (58%). Thirty-three patients (39%) received medical rescue therapy (17/33 IFX and 16/33 CIC). Colectomy rate during admission was 13% after a median duration of 18 days (IQR: 16-54). Admission C reactive protein (CRP) (p=0.036), albumin (p=0.026) and UCEIS scores (p=0.022) were significantly associated with steroid non-response. Patients scoring 0, 1, 2, 3 and 4 had steroid response rates of 90%,75%, 55%, 19% and 0%, respectively. Scoring of ≥3 was 75% (95% CI, 0.43 to 0.95) predictive of steroid failure (OR 5.08, 95%, CI 1.38 to 24.5).

Conclusion

In this tertiary referral cohort study, we confirmed that the ADMIT-ASC index is a simple clinical tool that can be used on the day of admission to predict steroid non-response in ASC with a threshold of ≥3 to identify patients who are unlikely to respond to intravenous CS and enabling timely treatment escalation or surgery.

References

1. Travis S, Satsangi J, Lémann M. Predicting the need for colectomy in severe ulcerativecolitis: a critical appraisal of clinical parameters and currently available biomarkers. Gut 2011;60:3–9.
2. Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis.Gut 1996;38:905–10.
3. Adams A, Gupta V, Mohsen W, et al. Gut 2023;72:433–442.

Disclosure

VB has not disclosure.
CDT has not disclosure.
CM has not disclosure.
AC has received lecture fees from Galapagos, Abbvie, Janssen, celltrion, Pfizer, Takeda.
DF has received lecture fees from Abbvie, Astrazeneca, Dr.Falk Pharma, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, Amgen, and advisory board fees from Abbvie, Janssen,Takeda, Celltrion, Amgen.
CL has received consultancy fees from Janssen, Abbvie, Takeda and Galapago and speaker fees from Sandoz, Janssen, Abbvie

Introduction

Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common gastroenterological emergency associated with significant morbidity and mortality [1-3]. Upper gastrointestinal endoscopy is currently recommended as the gold standard modality for both diagnosis and treatment [4]. As historically played a limited role in the diagnosis of acute NVUGIB, multidetector-row computed tomography angiography (MDCTA) is emerging as a promising tool in the diagnosis of NVUGIB, especially for severe cases [5-6]. However, to date, evidence concerning the role of MDCTA in the NVUGIB diagnosis is still lacking.

Aims & Methods

The purpose of this study was to retrospectively investigate the diagnostic performance of emergent MDCTA performed prior to any diagnostic modality or following urgent upper endoscopy to identify the status, the site and the underlying etiology of severe NVUGIB. Institutional databases were reviewed in order to identify severe acute NVUGIB patients who were admitted to our bleeding unit and were referred for emergent MDCTA prior to any hemostatic treatment (<3 hours) or following (<3 hours) endoscopy, between December 2019 and October 2022. The study aim was to evaluate the diagnostic performance of MDCTA to detect the status, the site and the etiology of severe NVUGIB with endoscopy, digital subtraction angiography, surgery, pathology or a combination of them as reference standards.

Results

A total of 68 patients (38 men, median age 69 years [range 25–96]) were enrolled. The overall MDCTA sensitivity, specificity, and accuracy to diagnose bleeding status were 77.8% (95% CI: 65.5-87.3), 40% (95% CI: 5.3-85.3), and 75% (95% CI: 63.0-84.7), respectively (Table 1). Finally, the overall MDCTA sensitivity to identify the bleeding site and the bleeding etiology were 92.4% (95% CI: 83.2-97.5) and 79% (95% CI: 66.8-88.3), respectively.

Table 1. The diagnostic performance of MDCTA in detecting bleeding status.

	Active (n = 40)	Recent (n = 26)	Non-active and non-recent (n = 2)	Total (n = 68)
TP	29	20	-	49
TN	-	-	2	2
FP	0	3	-	3
FN	11	3	0	14
Sensitivity (95% CI)	72.5 (56.1-85.4)	87.0 (66.4-97.2)	-	77.8 (65.5-87.3)
Specificity (95% CI)	-	-	100 (15.81-100)	40.0 (5.3-85.3)
PPV (95% CI)	100 (88.1-100)	87.0 (66.4-97.2)	-	94.2 (84.1-98.8)
NPV (95% CI)	-	-	100 (15.81-100)	12.5 (1.55-38.4)
Accuracy (95% CI)	-	-	-	75 (63.0-84.7)

TP, true positive; TN, true negative; FP, false positive; FN, false negative; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value.

Conclusion

MDCTA seems to be a feasible and effective modality in detecting the site, the status and the etiology of severe acute NVUGIB. It may play a crucial role in the management of selected cases of NVUGIB, especially those clinically severe and/or secondary to rare and extraordinary rare sources, effectively guiding timing and type of treatment. However, further large prospective studies are needed to clarify the role of MDCTA in the diagnostic process of acute NVUGIB.

References

1. Wuerth BA, Rockey DC. Changing Epidemiology of Upper Gastrointestinal Hemorrhage in the Last Decade: A Nationwide Analysis. Dig Dis Sci 2018; 63: 1286–1293.
2. Laine L, Yang H, Chang S-C, et al. Trends for incidence of hospitalization and death due to GI complications in the United States from 2001 to 2009. Am J Gastroenterol 2012; 107: 1190–1195; quiz 1196.
3. Sanders DS, Perry MJ, Jones SGW, et al. Effectiveness of an upper-gastrointestinal haemorrhage unit: a prospective analysis of 900 consecutive cases using the Rockall score as a method of risk standardisation. Eur J Gastroenterol Hepatol 2004; 16: 487–494.
4. Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021. Endoscopy 2021; 53: 300–332.
5. Napoli A, Fleischmann D, Chan FP, et al. Computed tomography angiography: state-of-the-art imaging using multidetector-row technology. J Comput Assist Tomogr 2004; 28 Suppl 1: S32-45.
6. Wu L-M, Xu J-R, Yin Y, et al. Usefulness of CT angiography in diagnosing acute gastrointestinal bleeding: a meta-analysis. World J Gastroenterol 2010; 16: 3957–3963.

Disclosure

No conflict of interest to declare.

Introduction

Rectal sensory function plays a critical role in normal bowel function. For example, rectal hypersensitivity is associated with Irritable Bowel Syndrome (IBS), whereas rectal hyposensitivity is linked to constipation.
The International Anorectal Physiology Working Group (IAPWG) (1) has established a standardised investigation protocol for anorectal physiological function. According to this protocol, the rectal sensory function is evaluated by simple balloon distension using an elastic balloon during a standard high-resolution anorectal manometry investigation (HRAM). However, the gold standard for rectal sensory assessment is the rectal barostat investigation, as described by the European COST action GENIEUR group (2).
The correlation between these two methods is largely unknown. The two methods use different balloons (elastic vs. non-elastic balloons, different size and shape). Moreover, the barostat is pressure-controlled whereas the HRAM is volume-controlled. For this reason, assessment of the level of agreement is not feasible.

Aims & Methods

We assessed the correlation between rectal sensory testing with the HRAM and rectal barostat investigations for each sensory threshold, in a group of healthy volunteers.
Twenty-six healthy volunteers (mean age 42 years, 50% females) were recruited and investigated using both HRAM according to the IAPWG protocol and rectal barostat using the GENIEUR protocol on the same day.
Sensory thresholds for first sensation (FS), first urge (FU), intense urge (IU) and maximum tolerable volume (MTV) were recorded for both methods.
Spearman’s rank correlation coefficient was used for analysis, since it does not assume normal distribution.

Results

Median values, along with the 1^st and 3^rd quartile are presented in Table 1.
There were statistically significant positive correlations between the sensory thresholds for first urge, intense urge and maximum tolerable volume. However, the correlation coefficients were generally weak, with only MTV showing a correlation coefficient above 0.5.

Table 1. Quartiles of the four sensory thresholds used and Spearman’s correlation factor between HRAM and barostat based investigations.

	First sensation		First urge		Intense urge		MTV
Quartiles	HRAM	B	HRAM	B	HRAM	B	HRAM	B
1st	12.00	43.00	60.25	91.75	86.25	155.00	116.75	189.25
2nd	27.50	76.00	79.00	142.50	111.50	210.00	175.50	230.50
3rd	48.75	108.00	96.00	177.00	164.50	259.50	224.75	319.00
Spearman’s rho	.151		.433		.400		.573
p	.460		.026		.043		.002

Conclusion

There is a weak correlation between the two methods, suggesting that HRAM balloon distension and barostat cannot be used interchangeably with respect to rectal sensory testing. Standardisation of rectal sensory testing is warranted to improve the accuracy and reliability.

References

(1). Carrington E. et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterology & Motility. 2020;32: e13679.
(2). https://genieur.eu/Downloads/PhenotypingTool/SOP_Rectal_barostat.pdf

Introduction

Postoperative ileus, is one of the most common causes of prolonged hospital stays after abdominal surgery which cause from physiologic hypomotility of the gastrointestinal tract occurring immediately after abdominal surgery. Multi-modal approach to the resolution of postoperative ileus includes ERAS protocol such as opioid minimization, early ambulation, intake of prokinetic drug. Mosapride citrate (mosapride) is known to promote gastrointestinal motility. The objective of this study is to evaluate the effects of mosapride on postoperative ileus and postoperative gastrointestinal motility in patients undergoing elective open and laparoscopic colorectal surgery.

Aims & Methods

The study was approved by ethics committee of the Faculty of Medicine Ramathibodi Hospital Mahidol University (Ref. Number COA.MURA2021/328,ClinicalTrials.gov Identifier: NCT04905147). Forty-four colorectal cancer patients, undergoing open and laparoscopic colorectal surgery in Ramathibodi Hospital during July 2021-August 2022, were randomly assigned to a mosapride group or control group. The mosapride group received 15 mg of mosapride by enteric route with 50 ml of water three times a day, starting on postoperative day 1. The control group received 15 mg of placebo drug with 50 ml of water at the same time. Postoperative time to the first passage of flatus and the first bowel movement were evaluated by one investigator with triple blind study. Time to step diet, length of postoperative hospital stays, and adverse effects were also evaluated in secondary outcomes.

Results

All forty four patients were include, twenty-three in control group and twenty-one in mosapride group. There were no statistically significance differences between mean age and type of surgery (laparoscopic or open) in two group (P>0.05). Time to first bowel movement and time to passage of flatus after operation were significantly shorter in the mosapride group than the control group (26 vs 50 hours, P=0.004 and 40 vs 70 hours, P=0.003, respectively). Time to step diet (soft diet) was also shorter in the mosapride group (90 vs 132 hours, P=0.004). Time to defecate was less in mosapride group than control group (80 vs 120 hours, P <0.001). Length of hospital stay was significantly shorter in patients receiving mosapride (7 vs 10 days, P=0.004).

Conclusion

This study demonstrated the efficacy of mosapride when administered to patients who underwent elective colorectal surgery. Mosapride significantly enhance recovery of gastrointestinal motility and shorter length of hospital stay with no significant adverse effects.

References

1. Collins TC, Daley J, Henderson WH, Khuri SF. Risk factors for prolonged length of stay after major elective surgery. Ann Surg 1999;230:251–9
2. Vather R, O'Grady G, Bissett IP, Dinning PG. Postoperative ileus: mechanisms and future directions for research. Clin Exp Pharmacol Physiol. 2014;41(5):358-370.
3. Goldstein JL, Matuszewski KA, Delaney C, Senagore A, Chiao E, Shah M, et al. Inpatient economic burden of postoperative ileus associated with abdominal surgery in the United States. P AND T.2007;32(2):82.
4. Venara A, Neunlist M, Slim K, Barbieux J, Colas PA, Hamy A, et al. Postoperative ileus: Pathophysiology, incidence, and prevention. J Visc Surg 2016;153:439-46.
5. Luckey A, Livingston E, Taché Y. Mechanisms and Treatment of Postoperative Ileus. Arch Surg. 2003;138(2):206–214.
6. Georgiadis, G & Markantonis, Sophia & Triantafillidis, John. (2000). Prokinetic agents: Current aspects with focus on cisapride. Annals of Gastroenterology. 13.
7. Reynolds, J.C. & Putman, P.E. (1992) Prokinetic Agents, Gastroenterol Clin of North Am, Vol.21, pp.567-596.
8. Taniyama, K., Makimoto, N., Furuichi, A. et al. Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine₄ receptor, in gastrointestinal motility. J Gastroenterol 35, 575–582 (2000).

Introduction

Thiopurines are one of the major drugs for inflammatory bowel disease. In Asian individuals, the SNP p.Arg139Cys in exon 3 of NUDT15 is associated with leucopenia and hair loss.

Aims & Methods

The aims of this study are to evaluate the long-term effects of NUDT15 on clinical outcomes.
The patients (ulcerative colitis130, Crohn’s disease 55 cases) were divided into the mutant and the wild group of NUDT15, and the daily dosage of thiopurines and the effect of the mutation on hospitalization and surgery were investigated.

Results

Compared to the mutant group (n = 48), the daily thiopurine dosage increased in the wild group (n = 137)(p = 0.024). The time to dose reduction and discontinuation of thiopurine was significantly shorter in the mutant group, respectively (p < 0.001, p = 0.039). The mutant group tended to have more hospitalizations (p = 0.067), and surgeries were significantly more frequent (p = 0.028). In ulcerative colitis, thiopurine discontinuation was associated with hospitalization and surgery, respectively (p = 0.003, HR 2.87, 95% CI 1.44 - 5.71, p = 0.036, HR 5.45, 95% CI 1.12 - 26.5). In Crohn's disease, the presence of SNPs was associated with hospitalization (p = 0.019, HR 3.68, 95% CI 1.24-10.97) and surgery (p = 0.036, HR 6.81, 95% CI 1.14 - 40.86).

Conclusion

In ulcerative colitis, it is important to continue thiopurine with fine-tuning of the dosage to avoid hospitalization and surgery. In Crohn's disease, a direct association between the NUDT15 SNP and hospitalization and surgery was demonstrated.

References

1. Yang, S. K. et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet 46, 1017-1020, doi:10.1038/ng.3060 (2014).
2. Kojima, Y. et al. Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines. World J Gastroenterol 24, 511-518, doi:10.3748/wjg.v24.i4.511 (2018).
3. Coenen, M. J. H. et al. Identification of Patients With Variants in TPMT and Dose Reduction Reduces Hematologic Events During Thiopurine Treatment of Inflammatory Bowel Disease. Gastroenterology 149, 907-917.e907, doi:10.1053/j.gastro.2015.06.002 (2015).
4. Hirotsu, Y. et al. Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing. Mol Genet Genomic Med 3, 121-129, doi:10.1002/mgg3.120 (2015).
5. Sakamoto, I. et al. BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer. Cancer 122, 84-90, doi:10.1002/cncr.29707 (2016).
6. Hirotsu, Y. et al. Intrinsic HER2 V777L mutation mediates resistance to trastuzumab in a breast cancer patient. Med Oncol 34, 3 (2017).
7. Hirotsu, Y. et al. Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer. Mol Genet Genomic Med 3, 459-466 (2015).

Disclosure

The authors have no conflict of interest to declare. All co-authors have seen and agree with the contents of the manuscript, and there is no financial interest to declare.