Introduction

With disease progression, patients with chronic pancreatitis experience pancreatic exocrine insufficiency (PEI), nutritional deficiencies with associated bone complications and impaired quality of life.

Aims & Methods

The aim of this study was to investigate risk factors in patients with chronic pancreatitis and to evaluate their relation to bone density complications. The severity of CP was assessed by the M-ANNHEIM classification. Nutritional status was evaluated by fat-soluble vitamins D (CMIA method) and K (K1 and K2 by High-Performance Liquid Chromatography); magnesium and BMI in addition to routine biochemical markers; PEI was assessed by fecal-elastase-1, and imaging morphological data by Cambridge classification for CT/MRCP (grade I-IV). Bone densitometry was performed by Dual-energy X-ray absorptiometry. For statistical analysis was used SPSS v22.

Results

The study enrolled 45 patients with chronic pancreatitis (29 males, 52,01 ± 14,42). Patients with severe morphological changes (25 patients) were evaluated with lower vitamin D (р = 0,04) and K1 levels (р = 0,027). PEI with fecal elastase-1 values below 200 μg / g feces was found in 17 patients. The mean levels of vitamin D, K1, and K2 were 37.85 nmol/L 0.21 μg / L, and 0.15 μg / L, respectively. Vitamin D deficiency was found in 10 patients and insufficiency in 22 patients. 11 patients had low vitamin K levels. Significantly higher vitamin D values were observed with increasing BMI (r = 0.39, p = 0.001). Disease progression by M-ANNHEIM classification was associated with lower vitamin D and K levels. Osteopenia was observed in 10 patients and osteoporosis in 6 patients. Bone density was affected and significantly decreased in patients with vitamin D deficiency or severe insufficiency, PEI, and morphological changes grade Cambridge IV (p < 0.05).

Conclusion

An effort should be the point of a multidisciplinary approach for an up-to-date strategy for patients with pancreatic disorders. Proper patients follow-up and monitoring of complications of chronic pancreatitis might reduce the associated morbidity and mortality and ensures a better quality of life.

Introduction

Recurrent abdominal pain is the predominant symptom of chronic pancreatitis (CP), contributing to significant morbidity and reduced quality of life. Medical management includes analgesics, antioxidants, neuromodulators, and pancreatic enzyme replacement therapy (PERT). While PERT is used for pancreatic exocrine insufficiency (PEI), it is also thought to reduce pain by suppressing pancreatic secretion via negative feedback. However, previous meta-analysis did not show pain reduction, though subgroup analysis suggested potential pain relief with non-enteric (NE) coated enzymes1. Unlike currently available enteric-coated formulations, high in lipase but low in proteas, non-enteric coated enzymes with high protease content dissolve rapidly and may more effectively suppress cholecystokinin-mediated pancreatic stimulation, potentially improving pain outcomes.

Aims & Methods

To primarily assess the effect of a high-protease, non-enteric-coated pancreatic enzyme preparation on pain in patients with painful chronic pancreatitis. The study was registered under ClinicalTrials.gov (NCT05042284).
We conducted a randomized, double-blind, placebo-controlled trial where we randomly assigned participants to a high protease (30,000 U)-containing, non-enteric-coated enzyme preparation (n=54) and a placebo (n=53) group. The study duration was 24 weeks. Patients with painful CP (per Mayo Clinic criteria) with chronic pain were enrolled. The primary outcome was to see a difference in mean Izbicki pain score at 12 and 24 weeks and a change in pain scores (VAS 0-10) using pain diaries. Secondary outcomes were changes in the number of painful days, analgesic requirements, patient’s global impression of change (PGIC), quality of life, and adverse effects. Weekly pain data were collated. Repeated measures, linear, and mixed-effects models were used to analyze the primary outcome. Analysis was intention-to-treat.

Results

107 out of 256 screened patients fulfilled enrollment criteria. The mean age was comparable between groups (35.1±10.6 vs. 33.6±12.3 years; p=0.51), and baseline characteristics were similar. The primary outcome using mixed model analysis showed no significant differences in the change in Izbicki pain scores between the two groups at 12 and 24 weeks (Table: Results). The mean difference in VAS pain score was -3.7(95%CI: -4.3to-3.1) in enzyme group vs. -3.5(95%CI: -4.2to-2.9) in placebo group (p=0.64) at 12 weeks. The changes were -4.2(95%CI: -4.7to-3.6) vs. -4.1(95%CI: -4.7to-3.5), respectively (p=0.79), at 24 weeks indicating no significant difference. The median number of painful days was also similar, at 12 weeks, 16 (IQR: 9–35) in the enzyme group vs. 16 (IQR: 4–36.5) in placebo (p=0.31); at 24 weeks, 3(IQR: 0–8.5) vs. 3(IQR: 0–7)(p=0.30) respectively. Analgesic use was higher in the enzyme group at 12 weeks (45(83.3%) vs. 37(69.8%); p=0.11) and 24 weeks (42(77.8%) vs. 35(66%); p=0.20). Differences in the change in global health status, quality of life, PGIC, and adverse effects at both time points were also non-significant.

Conclusion

Despite the high protease content, Non-enteric coated enzyme preparations did not improve pain and quality of life in patients with painful chronic pancreatitis. Further RCTs are needed to evaluate benefits in distinct subgroups.

References

1. Yaghoobi, Mohammad, Julia McNabb-Baltar, Raheleh Bijarchi, and Peter B. Cotton. “Pancreatic Enzyme Supplements Are Not Effective for Relieving Abdominal Pain in Patients with Chronic Pancreatitis: Meta-Analysis and Systematic Review of Randomized Controlled Trials.” Canadian Journal of Gastroenterology and Hepatology. Doi: https://doi.org/10.1155/2016/8541839

Introduction

Cholangioscopy-assisted intraductal lithotripsy is a first-line option in the treatment of complex gallstones. Its effectiveness and safety are demonstrated in the literature by multiple studies published after 2017.
However, there are no published studies about the long-term recurrence of choledocholithiasis in patients treated by these techniques.
With this study we intend to answer this question, evaluating the long-term recurrence of choledocholithiasis in patients with complex choledocholithiasis treated with intraductal lithotripsy techniques.

Aims & Methods

Retrospective cohort study of 62 consecutive patients who underwent cholangioscopy-guided intraductal lithotripsy between 2017 and 2022 at our center. Data were collected from a dedicated prospectively maintained database.
Primary outcome: recurrence of choledocholithiasis. Follow-up time: 5 years.
Survival analysis was performed using Kaplan-Meyer curves and Cox regression (Statistical software STATA 17 (StataCorp, TEXAS).

Results

Of the 62 patients, 35 (56.5%) were women, mean age 72 years (min. 28, max. 96), 20 of whom had previously undergone cholecystectomy and with a mean follow-up time after lithotripsy of 28.21 months . 88.7% of patients achieved complete stone removal in the 1st session, with a rate of 100% at the second procedure. The mean number of stones was 2.02 with a size of 18.74mm. There was recurrence of choledocholithiasis in 9 patients, of which 77.8% had cholangitis, with a mean time of 13.33 months after lithotripsy. In patients with recurrence of choledocholithiasis, 22.2% had gallbladder. None of the patients required surgery to explore the biliary tract.

Conclusion

Cholangioscopy-guided lithotripsy is associated with a high success rate in difficult gallstones, with a safety profile similar to conventional techniques and lower rates of choledocholithiasis during follow-up.

Introduction

Per-oral cholangioscopy (POC)-targeted biopsies, potential to overcome the problems associated with inadequate tissue sampling and increase the diagnostic sensitivity of bile duct nodular tumors. The utility of frozen section analysis, able to detect malignancy immediately and allows the early surgery in patients with invasive carcinoma.

Aims & Methods

To evaluate the diagnostic yield and efficiency of POC-targeted biopsies combined with frozen section histopathology.
From Oct. 2017 to Dec. 2021, consecutive patients with biliary nodular tumors were included in this study. The cholangioscope (SpyGlass DS, Boston Scientific Co., Natick, MA, USA) was advanced through a standard therapeutic duodenoscope (Olympus). All procedures were performed under moderate sedation or general anesthesia. Before POC, a standard endoscopic retrograde cholangiogram (ERC) with biliary sphincterotomy was performed to localize the bile duct nodular tumor and to facilitate ductal access and therapy. The cholangioscope was introduced into the bile duct through a guidewire via the working channel. The biliary trees were inspected, and suspicious lesions are biopsied. No more than nine biopsies per lesion were taken for histological examination. The specimens of endoscopic biopsies were then sent to the frozen section laboratory for freezing and staining. The slides were read immediately, and a preliminary report was conveyed to the clinician. The pathologist would then assess for the presence or absence of dysplasia or invasive cancer in the specimen.

Results

A total of 8 patients (7 male and 1 female; mean age 65 years) with bile duct nodular tumors undergoing cholangioscopy-targeted biopsies with frozen sections were included. The clinical presentations of the patients were obstructive jaundice 2, abdominal pain 2, and imaging findings 4. Seven of the 8 patients had undergone ERC and ductal biopsies without definite diagnosis. The nodular tumors in the bile ducts, average size 1.5 cm (range 0.8-2.0), were located in proximal (4), middle (1) and distal (3) extrahepatic duct respectively. Among 8 patients with biopsy-proved malignancy, 3.5 times (range 2-9) biopsies were needed to be taken. All except one frozen section histopathology (adenocarcinoma in situ) was not compatible with surgical pathology (high grade dysplasia). Hilar invasion was observed in one patient during cholangioscopy, and subsequently surgery was not performed. One patient developed severe complication associated with acute cholangitis.

Conclusion

In this case series study, combined POC-targeted biopsies with frozen section histopathology provides an immediate and efficient diagnosis and allows an early surgery for patients with bile duct tumors. More patients are need to be included in the further study.

Disclosure

Nothing to disclose

Introduction

The evaluation of intraductal extension of perihilar cholangiocarcinoma (pCCA) is extremely challenging and affects the resectability of the disease. Digital Single-Operator Cholangioscopy (D-SOC) and D-SOC-guided biopsies are frequently used for diagnostic assessment of indeterminate biliary strictures.

Aims & Methods

In this study, we evaluated the role of D-SOC and D-SOC-guided biopsies in the pre-operative evaluation of intraductal extension of pCCA. We retrospectively analysed pCCA patients who underwent D-SOC and D-SOC-guided biopsies to assess the intraductal extension of the tumor prior to surgery for potentially resectable disease in our center between 2017 and 2021. The accuracy of endoscopic appearance and histological sampling were compared to surgical samples obtained at surgery.

Results

Among 48 patients who underwent surgery for pCCA, after multidisciplinary discussion, D-SOC and D-SOC-guided biopsies were performed for proximal biliary staging in 6 patients (M:F 5:1, mean age at diagnosis 67 y.o.), which had an unclear ductal extension. A total of 12 D-SOC -guided biopsies were performed (7 from common duct, 2 from right duct and 3 from left duct). Concordance between CS-guided biopsies and surgical samples histological evaluation was 83% (10/12), with 6/6 true positives, 4/6 true negatives and 2/6 false negatives. Among the histological false negatives, the first case had a cholangioscopic appearance compatible with CCA extension, thus the result of D-SOC-guided biopsies did not influence the therapeutic choice. In the second histological false negative, the evaluation of the surgical specimen showed perineural invasion and periductal tumor development. Radical surgery was achieved in all 6 patients.

Conclusion

Despite limited sample size, our preliminary data suggest a very high specificity of D-SOC and D-SOC -guided biopsies in the pre-operative evaluation of intraductal extension of potentially resectable pCCA patients. A multidisciplinary approach and an accurate pre-operative assessment of pCCA remain of paramount importance to correctly diagnose and stage the disease before surgery.

Introduction

In superficial gastric tumors, endoscopic submucosal dissection (ESD) has become the standard of care, and the treatmenttechnique and strategy have been matured. On the other hand, the number of cases performed by trainees as anintroduction to ESD is increasing, and the types and handling of antithrombotic drugs are also changing.

Aims & Methods

On these backgrounds, we examined the transitions to clarify how the treatment outcomes and adverse events of gastric ESD have changed.
From 2014 to 2022, 565 patients of superficial gastric neoplasms who underwent ESD were divided into two groups: the first half (n=435) from 2014 to 2020 and the second half (n=130) from 2021 to 2022, where the number of trainees significantly increased. Treatment outcomes (En bloc resection rate, curability, procedure time, inflammatory response)and adverse events (perforation, postoperative bleeding, postoperative pneumonia, and pyrexia for unknown reasons) were retrospectively compared between two groups, using the propensity score matching analysis. Regarding oral antithrombotic agents, antithrombotic drugs were continued, DOAC stopped only 24 hours before treatment, and warfarin was continued after INR value was controlled at <3.0.

Results

Propensity score matching yielded 130 pairs. Trainee's involvement was 29.7% in the first half and 61.4% in the second half. The comparison demonstrated a significant difference for the following outcomes: curability was 86% in the first half and 90.1% in the second half (P=0.028), the CRP mean [SD] was 1.32 [2.14] in the first half and 0.82 [0.97] in the second half (P=0.032), and postoperative bleeding rate was 5.9% in the first half and 0.0% in the second half (P=0.013). Others were similar values for outcomes.

Conclusion

Even with the increased involvement of trainees, treatment outcomes have not chronologically exacerbated. Additionally, inflammatory response and postoperative bleeding have improved. These results suggest that safe and secure gastric ESD can be performed by appropriate technique and strategy under supervise of experts.