Introduction

Gastroenterology is a medical specialty that includes several areas of study. Endoscopy occupies a central role in professional practice, whether in hospitals or in the private sector. The quality of initial training and the different needs of trainees are key to the quality of care delivered to the population. This study aims to assess endoscopic training experience during fellowship.

Aims & Methods

This is a cross-sectional, multicenter study conducted on gastroenterology residents practicing endoscopy and in the final phase of their curriculum (6th, 7th and 8th semesters). Postgraduated doctors have been excluded from the study. An electronic survey made by Google Forms and was sent nationwide on January 9, 2024. The survey consisted of 42 questions divided into 3 parts: The first part focused on the participants' socio-demographic data and their endoscopic experience, the second part focused on the quality of training of core endoscopic skills (cognitive and motor skills) during fellowship where a 5-point Likert scale was used to express residents' satisfaction with their skills, ranging from 1="very dissatisfied", 2="dissatisfied", 3="neither satisfied nor dissatisfied", 4="satisfied" and 5="very satisfied". The third part included questions in which participants expressed their needs and expectations for improving their training in endoscopy. A statistical analysis using the Student-t test and the Fisher’s exact test were performed. P values of <0.05 were considered statistically significant. Data were analyzed using Jamovi (Version 2.3).

Results

We were able to collect data from 56 respondents. Most were female residents n=40 (71.4) with a mean age of 29.2 ± 2.5 years. The majority of fellows started practicing EGD in their 4th semester (91.1%), and colonoscopy in their 6th semester (57%). On average, the fellows are supervised by 5 senior doctors, including 2 who practice interventional endoscopy. Furthermore, 37.5% of participants report performing approximately more than 100 EGDs, 14.2% more than 100 colonoscopies, 80.4% report that they have performed less than 20 endoscopic variceal ligation and 14.3% have performed more than 10 polypectomies. An average rating score of 3.34 (1= very dissatisfied; 5= very satisfied) concerning the quality of training and feedback on cognitive aspects of endoscopy was found and we reported greatest emphasis for Procedure indication/contraindication and least on Capsule endoscopy interpretation.
The quality of training in technical aspects of endoscopy was rated higher (average rating score of 3.5). We reported greatest emphasis for Withdrawal/mucosal inspection and least on Esophageal dilation.
A significant association between motor skills and cognitive skills was found with a p<0.001.
Finally, to improve their training, 87.5% of respondents considered simulation to be important/very important, 98.2% of respondents intend to complete their endoscopy training at the end of their curriculum, and 87.5% are prepared to finance such a project (median: 1000 USD [1000;3000]).

Conclusion

Despite a significant improvement in training sites and technical facilities, training in endoscopy in healthcare institutions does not yet provide all the cognitive and technical skills required to enable fellows to be fully autonomous. With the development of endoscopic procedures, it seems essential for fellows to be able to perform more standard endoscopic procedures such as polypectomy and mucosectomy by the end of their curriculum. This may involve introducing regular endoscopy conferences and simulation training as a part of the curriculum.

Introduction

Endoscopic submucosal dissection (ESD) is a highly effective and safe technique for the resection of superficial colorectal neoplasms, but it can still be technically challenging for lesions in contact with or invading the appendiceal orifice. Until recently, appendicular lesions were considered unresectable or difficult to resect by endoscopy because of the high risk of incomplete resection, perforation or acute appendicitis. Small studies have reported ESD feasibility and efficacy in this particular context, including for lesions deeply invading the appendix. However, strong data about these more complex resections is lacking and the best management strategy for this kind of lesion remains a matter of debate, with upfront surgery still being the first-choice treatment in most western countries.

Aims & Methods

With the present study, we aimed to assess and report the outcomes of ESD for the treatment of lesions in contact with or invading the appendiceal orifice. We prospectively collected data of ESD procedures for appendiceal neoplasia in a multicenter prospective register. En Bloc R0 resection rate was the primary outcome. Morbidity and additional surgery were also reported.

Results

A total of 112 patients were included, comprising 47 (42%) with previous appendectomy. Fifty-six lesions (50%) were type 3 according to Toyonaga classification (15 (13.4%) post-appendectomy). En-bloc and R0 resection rates were 86.6% and 80.4%, with no significant difference associated with different grades of appendiceal invasion (p=0.9 and p=0.4, respectively) or history of previous appendectomy (p=0.3 for both). Curative resection rate was 78.6%. Additional surgery was performed in 16 (14.3%) cases, with 10/16 (62.5%) corresponding to Toyonaga type 3 lesions (p=0.04). This included the treatment of 5 (4.5%) cases of delayed perforation and 1 acute appendicitis. A second case of acute appendicitis and 1 of delayed hemorrhage also observed, both treated conservatively.

Conclusion

To our knowledge, this is the largest reported series of ESDs for the treatment of appendicular lesions. Our results show that ESD is safe and effective in this context, and should thus be considered as a valuable treatment option. New traction strategies and devices should make it progressively less technically challenging and more widely accessible.

Introduction

Ozanimod (OZA) is approved for the treatment of moderately to severely active ulcerative colitis and relapsing multiple sclerosis. A previous phase 1 study of single dose OZA 0.23 mg showed a 31%–33% reduction of CC112273, the predominant active metabolite (MET) of OZA, in mild or moderate hepatic impaired participants (ppts) vs healthy ppts. That study was designed prior to identification of the 2 major METs of OZA (CC112273; CC1084037). Due to their slow accumulation and elimination, a new multiple dose study was designed with a long sampling schedule.

Aims & Methods

This multicenter, open-label phase 1 study (NCT04639115) evaluated the effect of mild (Child-Pugh [C-P] score 5–6) or moderate (C-P score 7–9) hepatic impairment on the multiple-dose pharmacokinetics (PK) of OZA and its 2 major active METs. Eligible ppts with hepatic impairment without active hepatitis were enrolled into the mild or moderate hepatic impairment groups (8 ppts each) based on their C-P scores. Ppts with normal hepatic function were matched to hepatic-impaired ppts by sex, age, weight, and smoking status. All ppts received once-daily OZA for 8 d in accordance with dose titration: 0.23 mg on Days (D) 1–4, 0.46 mg on D5–7, and 0.92 mg thereafter. Serial PK samples were collected on D1, D5, and D8, and additionally on D10, D12, and D15, and up to D72. Analysis of variance (ANOVA) fitted to the natural log-transformed PK parameters with hepatic function group as the fixed effect and the matching pair as a random effect was used to compare PK parameters between groups. Safety was assessed.

Results

All dosed ppts (N=26) completed the study. Each hepatic impairment group had 8 ppts; 10 ppts were in the normal hepatic function group, of whom 6 matched both mild and moderate hepatic-impaired ppts. Of the 16 hepatic-impaired ppts, 13 had documented hepatic cirrhosis. No clinically meaningful differences in total and unbound PK parameters for OZA and its major METs were observed between healthy and hepatic-impaired ppts on D1, D5, or D8 (dose titration) (Table). The unbound area under the plasma concentration-time curve from D8, time 0 to the time of last quantifiable concentration (AUC_0-last) (up to 64 d after the D8 dose) of both METs increased ~2-fold in both mild and moderate hepatic-impaired ppts (Table). Although steady state for both METs was not achieved by D8, AUC_0-last is a reasonable predictor of exposure at steady state. No correlation was observed between PK parameters for OZA or its major METs and measures of hepatic function (C-P score, serum albumin, and prothrombin time). No laboratory results (ie, absolute lymphocyte count), vital signs, physical examination, or 12-lead ECG results were reported as treatment-emergent adverse events.

Conclusion

Due to the lack of OZA PK differences between hepatic-impaired and healthy ppts during dose titration and the 2-fold increase of AUC_0-last of both METs in hepatic-impaired ppts, a dose adjustment of OZA 0.92 mg once every other day is recommended in patients with mild or moderate hepatic impairment after completing the standard 1-week dose titration.

Disclosure

This study was funded by Bristol Myers Squibb, Princeton, NJ, USA.
PZ, FH, KY, SW, MS, GT, BM, and DT: employees and/or shareholders of Bristol Myers Squibb.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive endoscopic procedure that is crucial for pancreato-biliary diseases and selective cannulation is the most important step. However, even an experienced endoscopist can face cannulation failure in up to 15-30% of cases in the first ERCP when standard methods alone are used.¹ Many studies suggested the various needle knife fistulotomy or papillotomy as an alternative technique in difficult cannulation cases.^2,3 However, needle knife papillotomy (NKP), which is modified technique with needle knife has not been evaluated well.

Aims & Methods

To evaluate the clinical outcomes and adverse events of bile duct cannulation by NKP, we performed a retrospective review on medical records of all ERCP cases in Sheikh Khalfia Specialty Hospital, UAE. For six years, Sphincterotomy (SPT) naïve patients except altered-anatomy cases were enrolled and their procedure times, cannulation success rates, radiation exposures, and adverse events were measured between the procedure time matched two cohort group of SPT only and rescue NKP.

Results

In total 416 ERCP cases, 43 procedure time matched cases were selected among 352 (84.7%) SPT only cohort and 43 cases from 64 rescue NKP cohort. Biliary cannulation was succeeded in all cases (100%) by using SPT cannulation with rescue NKP technique without failure. There was no differences in cumulative radiation doses, cannulation time, and adverse event rates in rescue NKP group compared to SPT only group: Post-ERCP hyperamylasemia/hyperlipasemia (16.5% vs. 34.8%, p=0.080), pancreatitis (3.9% vs. 4.3%, p=0.883), cholangitis (4.7% vs. 4.3%, p=0.695), and no perforation case was noticed in both groups.

Conclusion

The SPT with rescue NKP technique can be used in the difficult biliary cannulation cases during ERCP safely and effectively.

References

(1) Testoni PA , Testoni S , Giussani A .
Difficult biliary cannulation during ERCP: how to facilitate biliary access and minimize the risk of post-ERCP pancreatitis.
Dig Liver Dis 2011;43:596–603
[2] Testoni PA , Mariani A , Aabakken L , Arvanitakis M , Bories E , Costamagna G,et al.
Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline.
Endoscopy 2016;4 8:657–6 83 .
[3] Lopes L , Dinis-Ribeiro M , Rolanda C .
Early precut fistulotomy for biliary access: time to change the paradigm of "the later, the better"?
Gastrointest Endosc 2014;80:634–641 .

Clinical Case Summary

A 68-year-old woman presented after 24 hours of painless jaundice, preceded by 48 hours of dark urine and pale stools without pruritis. No history of weight loss, recent foreign travel, or high risk behaviours. She denied any illicit drug or alcohol abuse. Her co-morbidities included pre-diabetes, and obesity and only took over-the-counter vitamin supplementation with no new or regular prescribed therapies. On clinical examination, she was fully alert with jaundice with no stigmata of chronic liver disease and haemodynamic stable.

Liver tests at presentation (normal in 2020) were ALT 766 U/L, AST 984 U/L, bilirubin 463, ALP 314 U/L. PT 35.3s, APTT 45.5s, TT 26.2s and albumin was 33 g/L. Haemoglobin (139 g/L), platelet count (158 x109/L), and normal eosinophil count (0.89 x109/L). Renal function was unremarkable. Arterial blood gas demonstrated a pH 7.4, Lactate 1.8, glucose 6. CT scan demonstrated moderate volume ascites and a grossly dilated gallbladder. No intra- or extra-hepatic duct dilatation and patent vasculature. Homogenous ANA 1:400, strongly positive SMA, polyclonal gammopathy (IgG 18.8, IgM 5.5, IgA 4.2) and negative AMA/ LKM. Viral hepatitis screen was negative. Given the severity of hepatic failure, she was referred for consideration of transplantation.

This lady presented with an acute hepatocellular pattern of liver injury with hepatic failure. It came to light that her injury was a consequence of exposure to ashwagandha. Although her exposure was in 2021, a latency period prior to drug-related injury is not unusual. Previous case series have shown similar patterns of injury with ashwagandha but no hepatic failure.

1. How do we overcome the challenges distinguishing drug-induced liver injury as a cause of acute hepatic failure, particularly when markers of alternative aetiology are present?
2. What is the role of steroids in patients ?
2. What is the relationship between DILI from herbal/ dietary supplementation and acute liver failure?

References

1. Katarey D, Verma S. Drug-induced liver injury. Clin Med. 2016;16(Suppl 6):s104-s109. doi:10.7861/clinmedicine.16-6-s104
2. Chalasani N, Bonkovsky HL, Fontana R, et al. Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study. Gastroenterology. 2015;148(7):1340-52.e7. doi:10.1053/j.gastro.2015.03.006
3. Paul S, Chakraborty S, Anand U, et al. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomed Pharmacother. 2021;143:112175. doi:10.1016/j.biopha.2021.112175
4. Mandlik Ingawale DS, Namdeo AG. Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects. J Diet Suppl. 2021;18(2):183-226. doi:10.1080/19390211.2020.1741484
5. Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. doi:10.1111/liv.14393