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

The densities of stem cells and their progenitors, and enteroendocrine cells are lower in IBS patients than healthy subjects.^1,2 IBS patients also exhibit submucosal low-grade inflammation.³

Aims & Methods

This study investigated the possible mechanisms underlying the effects of FMT in IBS patients included in a previous study from our group that showed high and long-term efficacy. Ninety-three patients who participated in our previous study were investigated: placebo group (24 patients), the groups that received 30g (47patients) or 60g (22 patients) donor`s transplant. The patients underwent sigmoidoscopy with biopsies, provided faecal samples, and completed IBS-symptom severity score (IBS-SSS), Fatigue Assessment Scale (FAS), and IBS Quality of Life questionnaires at the baseline and at 1 month after FMT. Sections from the biopsy samples were immune-stained for Musahi-1 (marker for stem cells and in their early progeny), neurogenin 3 (marker for early endocrine cell progenitors), chromogranin A (general marker for enteroendocrine cells), serotonin, peptide YY (PYY), glucagon-like peptide 1, GLP-1, pancreatic polypeptide, somatostatin, CD 45 (common marker for immune cells), B lymphocytes, T lymphocytes. NK cells, monocytes, macrophages, myeloid cells, and mast cells. The cell densities were quantified by computerized image analysis. Faecal short chain fatty acids (SCFAs) were measured by gas chromatography, and faecal bacteria by 16S rRNA PCR DNA amplification covering variable regions V3–V9.

Results

The densities of Musashi-1, neurogenin 3, chromogranin A, serotonin, PYY, and GLP-1 expressing cells increased significantly following FMT in patients who received 30g, or 60g transplant, but not in the placebo group. The densities of Musashi-1, neurogenin 3, chromogranin A, serotonin, and GLP-1 expressing cells correlated inversely with IBS-SSS total scores (r=-0.4, P<0.0001; r= -0.2, P=0.007; r=- 0.3, P<0.0001; r=-0.2, P=004; r=-0.4, P<0.0001, respectively). The densities of Musashi-1, chromogranin A, and GLP-1 also correlated inversely with FAS total scores (r=-0.2, P=0.01; r= -0.2, P=0.002; r=- 0.3, P=0.0009, respectively). The density of PYY cells did not correlate with either IBS-SSS or FAS scores. The densities of total submucosal immune cells, and mast cells decreased significantly after FMT in patients treated with 30g, or 60g donor´s faeces, but were unchanged in the placebo group. The densities of these cells were correlated positively with IBS-SSS total scores (r=0.4, P<0.0001; r=0.5, P<0.0001, respectively), and the total immune cells correlated with FAS total scores (r=0.3, P=0.0002). The levels of butyric acid increased significantly following FMT in the 30g and 60g treated groups, but not in the placebo group. The faecal levels of butyric acid were inversely correlated with IBS-SSS (r=-04. P<0.0001), and FAS (r=-0.3, P<0.0001) total scores. Among the bacteria that their abundance increased significantly in IBS patients that received FMT were Alistipes, Faecalibacterium prausnitzii, Eubacterium biforme and Lactobacillus spp.

Conclusion

Stem cells, enteroendocrine progenitor, serotonin, and GLP-1cells, as well as low-grade inflammation appear to play a significant role in IBS symptom manifestation and that FMT effect most probably is due to restoring the abnormality in them. The present observations suggest potential new treatments for IBS such as transplantation of epithelial organoids containing stem cells, GLP-1 agonist, low-dose anti-inflammatory drugs, pharmacological drugs to control mast cell function³, and sodium butyrate.

References

1-El-Salhy M. Possible role of intestinal stem cells in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2020;26:1427-1438.
2-El-Salhy M, Hausken T, Gilja OH, et al. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2017;11:139-148.
3-Barbara G, Stanghellini V, De Giorgio R, et al. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil 2006;18:6-17.

Disclosure

Nothing to disclose

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