Clinical Case Summary

Cholecystectomies are among the most commonly performed procedures worldwide, with about 1.2 million procedures being performed annually in the US. A complication rate of 0.5-2% has been reported. An iatrogenic clipping of the common bile duct (CBD), and right and left common hepatic ducts (R&LCHD) that would otherwise require a liver transplant was treated with a multidisciplinary approach by endoscopy and interventional (INT) radiology.
A 47-year-old female presented with jaundice after undergoing laparoscopic cholecystectomy for gangrenous cholecystitis. The patient’s R&LCHD, along with the mid-third area of the CBD were clipped during difficult surgery. The hepatobiliary surgeon recommended liver transplantation and the patient was waitlisted for transfer to a transplant center. An ERCP was performed to better understand the anatomy, the CBD was completely cut off at the middle portion due to surgical clips. A rendezvous procedure was recommended. The INT radiologist placed 2 PTBD drains in the R&LCHD. The endoscopist punctured the CBD near the clips to create a perforation and a basket was passed through the puncture site and wires were grasped from the R&LCHD drains and pulled into the duodenum. 10 French PTBD drains were placed in both the R&LCHD going through the CBD into the duodenum. The drains were exchanged for internal stents 8 weeks later. The stents were exchanged a few times and eventually removed completely as the patient found a neo-common bile duct around the initially placed PTBD drains.
Iatrogenic clipping of the CBD during surgery can have severe complications, requiring liver transplantation or hepaticojejunostomy. Placement of the percutaneous transhepatic internal and external stent can prevent a complex and high-risk surgical procedure. This case demonstrates an endoscopic and percutaneous approach to treat a bile duct injury that would have otherwise required liver transplant. The author has a series of 4 cases with successful outcomes.

References

Image 1. ERCP imaging revealing the clipped common bile duct Image 2. ERCP revealing PTBD drain placement after INT radiology and endoscopic procedure.

Introduction

Exocrine pancreatic insufficiency (EPI) may accompany primary exocrine pancreas diseases, such as chronic pancreatitis, which may also cause diabetes or develop as a complication.

Aims & Methods

The aim of this study is to determine the features of EPI in type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively), and its relationship with microvascular and macrovascular complications in these patients. Diabetic patients older than 18 years old (n=354) were evaluated at the beginning of study, and 166 were excluded due to diabetes duration less than 5 years (n=113), pregnancy status (n=27), presence of pancreatitis history (n=8), chronic alcohol consumption (n=6) and insufficient data (n=18). The patients’ demographic characteristics were determined. The macrovascular and microvascular complications of diabetes were evaluated through physical examination and biochemical analysis. EPI was evaluated through a fecal elastase-1 test.

Results

Of the study participants (mean age: 55.7±12.9 years; mean diabetes age: 16.6±7.9 years), 81.9% had T2DM, and 18.1% had T1DM. EPI was significantly higher in T2DM patients taking insulin than those who were not takin insulin (22.3% vs. 6.5%, p=0.020). Additionally, it was detected more frequently in diabetic patients with cardiovascular disease than those without cardiovascular disease (30.2% vs.14.4% p=0.02).

Conclusion

Exocrine pancreatic insufficiency is not rare among diabetic patients. The rate of EPI was higher in T1DM patients than in T2DM patients. T2DM patients taking insulin have more frequent EPI than T2DM patients not taking insulin. EPI should be taken into consideration in diabetic patients with cardiovascular complications as well as in T2DM patients who need insulin treatment.

References

1. Struyvenberg MR, Martin CR, Freedman SD. Practical guide to exocrine pancreatic insufficiency - Breaking the myths. BMC Med. 2017;15(1):29.
2. Radlinger B, Ramoser G, Kaser S. Exocrine Pancreatic Insufficiency in Type 1 and Type 2 Diabetes. Curr Diab Rep. 2020;20(6):18.
3. Singh VK, Haupt ME, Geller DE, Hall JA, Quintana Diez PM. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol. 2017;23(39):7059-7076.
4. Søfteland E, Poulsen JL, Starup-Linde J, et al. Pancreatic exocrine insufficiency in diabetes mellitus - prevalence and characteristics. Eur J Intern Med. 2019;68:18-22.
5. Barreto SG, Carati CJ, Toouli J, Saccone GT. The islet-acinar axis of the pancreas: more than just insulin. Am J Physiol Gastrointest Liver Physiol. 2010;299(1):G10-22.
6. Wei Q, Qi L, Lin H, et al. Pathological Mechanisms in Diabetes of the Exocrine Pancreas: What's Known and What's to Know. Front Physiol. 2020;11:570276.
7. Hardt PD, Ewald N. Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes? Exp Diabetes Res. 2011;2011:761950.

Introduction

Increasing infectious rate estimates and low microbiological surveillance affect safety of gastrointestinal endoscopy globally. Single use endoscopes and accessories have been claimed to improve safety, but there is lack of data on their indication and sustainability. We aimed to identify a series of best practice recommendations for the use of single use endoscopes and accessories using a modified Delphi.

Aims & Methods

Consensus statements for the use of single use endoscopy and accessories were developed using a modified Delphi process, utilizing an international endoscopist expert panel of 62 experts from 33 nations. The main steps in the process were selecting the consensus group, conducting systematic literature reviews, developing statements, and anonymous voting on the statements until consensus was reached. High-risk patients were defined as those with multi-drug-resistant infections, immunosuppressive medication or chemotherapy, post-transplantation, or with severe neutropenia.

Results

Twenty-six statements were voted upon through two rounds, the statements were categorised as single use accessories, clinical indication for single use endoscopes, technical factors, environmental issues, and financial implications addressing relevant areas of patient safety, infection, climate change and cost. Of the 26 statements, 17 statements reached consensus. Category 1: single use accessories (8 statements), related to defining recommendations for the use of single use accessories in all patient populations or high-risk patients. Category 2: clinical indication for single use endoscopes (9 statements), including indications to high-risk patients, protecting the endoscope apparatus and contamination measures in endoscopy units. Category 3: technical factors (4 statements), related to superior performance and technical specifications with the new innovation. Category 4: environmental issues (2 statements), concerning mechanisms that reduce the detrimental burden to the environment. Category 5: financial implications (3 statements), related to healthcare policies, cost neutrality and other financial associations of single use endoscopy.

Conclusion

This is the first international initiative in determining clinical indications for single use endoscopy and accessories. The study's findings should serve as a framework for future physicians to guide future research and aid the proper evidence-based indications for the implementation of single use endoscopes in clinical practice.

References

1. Kimmery MB, Burnett DA, Carr-Locke DL, DiMarino AJ, Jensen DM, Katon R, et al. Transmission Of Infection By Gastrointestinal Endoscopy. Gastrointest Endosc [Internet]. 1993;39(6):885–8. Available from: https://www.sciencedirect.com/science/article/pii/S0016510793703168
2. Ofstead CL, Dirlam Langlay AM, Mueller NJ, Tosh PK, Wetzler HP. Re-evaluating endoscopy-associated infection risk estimates and their implications. Am J Infect Control [Internet]. 2013;41(8):734–6. Available from: https://www.sciencedirect.com/science/article/pii/S0196655312013041
3. Kovaleva J, Peters FTM, van der Mei HC, Degener JE. Transmission of infection by flexible gastrointestinal endoscopy and bronchoscopy. Clin Microbiol Rev. 2013 Apr;26(2):231–54.
4. Kwakman JA, Erler NS, Vos MC, Bruno MJ. Risk evaluation of duodenoscope-associated infections in the Netherlands calls for a heightened awareness of device-related infections: a systematic review. Endoscopy. 2022 Feb;54(2):148–55.
5. Rauwers AW, Voor In ’t Holt AF, Buijs JG, de Groot W, Hansen BE, Bruno MJ, et al. High prevalence rate of digestive tract bacteria in duodenoscopes: a nationwide study. Gut. 2018 Sep;67(9):1637–45.
6. Gromski MA, Sherman S. Technological review: developments in innovative duodenoscopes. Gastrointest Endosc. 2022 Jan;95(1):42–50.
7. FDA. The FDA is Recommending Transition to Duodenoscopes with Innovative Designs to Enhance Safety: FDA Safety Communication [Internet]. FDA Safety Communication. 2021 [cited 2022 May 22]. Available from: https://www.fda.gov/medical-devices/safety-communications/fda-recommending-transition-duodenoscopes-innovative-designs-enhance-safety-fda-safety-communication

Disclosure

Cesare Hassan: Consulting fees for Fuji, and Medtronic. Alessandro Repici: Consulting fees for Fuji, Olympus, and Medtronic and receiving research grant and speaker fees from Boston Scientific, ERBE, Alfasigma, Norgine. Pradeep Bhandari: Research support from Fujifilm Europe, Boston Scientific, Pentax and Olympus Medical. Other authors declare no competing interests.

Introduction

Agonists and antagonists of G protein-coupled receptors (GPCRs) are widely used medications that serve in the therapy of constipation, diarrhea, and pain. However, little is known about how the effect of those drugs is modulated by Regulator of G Protein Signaling (RGS) proteins which promote timely silencing of the GPCR responses. RGS proteins have been documented to regulate the magnitude and duration of signals initiated by several types of GPCRs occurring in the GI tract, including opioid and cannabinoid receptors. Serving as a central control point in GPCR signaling cascades, RGS proteins hold great promises as targets for the drug development however their expression profile and function in the gut constitute a major gap in the knowledge.

Aims & Methods

The major emphasis of this study is on elucidating the expression and function of RGS proteins in physiology and pathophysiology of the GI tract. We hypothesize that identification of RGS proteins and GPCR signaling pathways that they control will reveal novel molecular targets combating GI disorders. METHODS: We used total RNA sequencing to evaluate the expression profile of RGS proteins in the mouse ileum and colon. Then we confirmed the expression of the most abundant transcripts with the qPCR and measured the expression of proteins with Western blot. Then in the in vivo conditions we used an RGS6 knockout (RGS-/-) mouse model to evaluate the effect of this protein on intestinal motility, pain and inflammation in naïve mice as well in the presence of the cannabinoid agonist WIN 55,212-2.

Results

RNA sequencing showed similar profile of expression of RGS proteins in the ileum and colon. qPCR analyses showed that Rgs2, 5 and 6 are the most abundant transcripts in the colon. At the level of protein we observed that RGS6 exhibits the highest expression in the ileum colon as well as intestinal intraepithelial lymphocytes. Moreover we observed a significant increase in RGS6 expression in the mouse colon samples during intestinal inflammation. In vivo experiments showed that RGS6-/- animals exhibit increased intestinal motility in physiological conditions and resistance to stress-induced diarrhea. Moreover RGS6-/- animals exhibit anti-nociceptive phenotype and are more susceptible to the analgesic effect of WIN 55,212-2. We did not observe the impact of RGS6 on the severity of colitis in the DSS-induced model.

Conclusion

Here we present RGS6 protein as a novel candidate for drug targeting in the GI tract. Our study suggests that loss and perhaps also pharmacological blockade of RGS6 might be used as standalone or an adjunct treatment to increase the potency of cannabinoids in the gut. The project is ongoing and further experiments are pending.

Introduction

The principal treatment option for treating chronic lymphoproliferative disorders (CLPD) is chemotherapy. The central concept in chemotherapy (CT) is adherence to the dose and drug administration regimens. It is impotent that infusion of CT agents in high doses is associated with an increased risk of chemotherapy-induced injury of the entire gastrointestinal tract (GIT).
The clinical manifestations of chemotherapy-induced mucositis are diarrhea. The presence of chemotherapy-induced injury mucositis can be assessed by the level of N-acetylneuraminic acid (NANA) and citrulline in the blood. The primary mechanism of the cytotoxic influence of CT agents is strongly associated with oxidative stress.

Aims & Methods

The aim is to investigate the effect of S-ademetionine on plasma NANA and citrulline levels in patients with CLPD during chemotherapy-induced injury The aim is to investigate the effect of S-ademetionine on plasma NANA and citrulline levels in patients with CLPD during chemotherapy-induced injury GIT.
Materials and methods: 24 patients with CLPD were examined (15 (75%) patients with B-cell chronic lymphocytic leukemia and 10 (25%) patients with Small B-cell non-Hodgkin lymphoma, 7 (28 %) females and 18 (72 %) males, ages 30-76. The inclusion criteria were the progression of B-CLL, Small B-NHL, and diarrheal syndrome on the background of CT. The examinations were conducted twice: before CT and after 3 courses of CT. Patients were analyzed the concentration of NANA in the blood, and the concentration of the citrulline in the plasma.
All patients received CT: BR (bendamustine, rituximab), FCR (fludarabine, cyclophosphamide, rituximab), R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). Depending on the inclusion of S-ademetionine as an adjuvant treatment, patients were divided into groups: І (n=13) – patients with CLPD, who received only CT. ІІ (n=14) – patients with CLPD, who received S-ademetionine at a dose of 1000 mg/day intravenously for 10 days, then 500 mg twice a day for 20 days. ІІІ (n=20) – the control group of 20 practically healthy individuals (9 (45 %) females and 11 (55 %) males, ages 22-26).

Results

Patients in both groups with CLPD had pre-existed mucosal injury characterized by 1.25 (p=0.0025) and 1.26 times (р=0.006) higher blood NANA concentration than the control group. The conduction of CT was associated with injury enterocytes, which was characterized by 1,66 times (p=0,0002) lower plasma citrulline level in patients of group I compared to the initial examination. The infusion of S-ademetionine attenuated intestinal dysfunction associated with 1,23 times (p=0,0005) higher blood citrulline level after the CT compared to group I.

Conclusion

The infusion of S-ademetionine as adjuvant treatment in patients with CLPD provided effective prophylaxis of GIT injury that was associated with higher blood citrulline levels after the conduction of CT.

Disclosure

No