Society: AGA

Background: Around 15% of acute pancreatitis patients develop necrosis of the pancreatic/peri-pancreatic tissue resulting in necrotic debris surrounded by a wall of granulation tissue called “walled-off pancreas necrosis” (WON). Patients with WON have a prolonged clinical course, often associated with infection within the necrotic debris. Direct endoscopic necrosectomy has been developed to remove the necrotic debris but is technically challenging due to the gluey debris and limited endoscopic accessories, requiring a median of 3-6 necrosectomy sessions for complete removal. Here, we aim to develop a chemical dissolution product to facilitate the breaking down and dissolution of the solid necrosome, allowing immediate aspiration in a single session.

Methods: Human pancreas necrosis specimens from endoscopic necrosectomies were collected and characterized using near-infrared spectroscopy to help identify candidate dissolution chemicals. The liquid dissolution chemicals were converted into a foam formulation to improve spreading within the WON cavity and contact with the debris. A novel endoscopic foam generation cap device was developed to deliver the dissolution foam through cyst gastrostomy (Fig.1). Ex-vivo high-throughput dissolution studies were performed on the porcine-pancreas necrosis model to optimize the foam formulation, requiring the lowest concentration of dissolution chemical and ensuring the stability of the foam (Fig.2). In-vivo porcine WON model was developed through implantation of the donor pancreas into the abdominal cavity of the recipient pig, to evaluate efficacy of dissolution foam and foam generation cap device. Safety studies were performed evaluating the effect of dissolution foam on granulation tissue wall, blood vessels, and gastric mucosa.

Results: Human pancreas necrosis debris characterization on spectrometry showed the presence of complex fats and proteins, nearly identical to the debris from the porcine pancreas necrosis model (p < 0.01). Hypochlorite (3.5%) based foam formulation with surfactants and stabilizing polymers showed >90% dissolution of necrotic debris at 10 mins, allowing complete suction through an endoscope (Fig.2). Stability testing of the foam formulation showed >95% intact bubbles at up to 18 hours. The in-vivo porcine study demonstrated adequate foam delivery through cyst gastrostomy opening (Fig. 2D). Safety studies showed no significant damage on gross and histopathological examination.

Conclusion: This novel foam formulation can chemically dissolve the WON necrotic debris in less than 10 minutes without damaging the granulation tissue wall or blood vessels and can be effectively delivered using our endoscopic foam generation cap device. This technology will potentially allow a single procedure complete necrosectomy avoiding the need for repeat interventions.

<b>Figure 1: A – </b>Foam generating cap that attaches to endoscope and converts injected solution into foam. <b>B – </b>In-vitro foam generation set-up to evaluate foaming from the dissolution solution, along with the cap attachment device. Peristaltic pump and gas source used to mimic endoscope.

Figure 1: A – Foam generating cap that attaches to endoscope and converts injected solution into foam. B – In-vitro foam generation set-up to evaluate foaming from the dissolution solution, along with the cap attachment device. Peristaltic pump and gas source used to mimic endoscope.

<b>Figure 2: A – </b>Ex-vivo dissolution study demonstrating complete dissolution of necrotic debris in < 10 mins and can be suctioned with an endoscope. <b>B – </b>Illustration of dissolution foam delivery into the necrotic cavity using cap attachment, through the cystgastrostomy. <b>C – </b>Custom 3D printed foam generation cap attachment prototype. <b>D – </b>In-vivo porcine study demonstrating the feasibility of foam delivery using the cap attachment, through cyst gastrostomy lumen-apposing metal stent.

Figure 2: A – Ex-vivo dissolution study demonstrating complete dissolution of necrotic debris in < 10 mins and can be suctioned with an endoscope. B – Illustration of dissolution foam delivery into the necrotic cavity using cap attachment, through the cystgastrostomy. C – Custom 3D printed foam generation cap attachment prototype. D – In-vivo porcine study demonstrating the feasibility of foam delivery using the cap attachment, through cyst gastrostomy lumen-apposing metal stent.

Background: Post-ERCP pancreatitis (PEP) is a common complication, that occurs in 5-10% of patients who first received Endoscopic retrograde cholangiopancreatography (ERCP). Recently, the efficacy of early refeeding for acute pancreatitis (AP) has been reported, however, the effect of early refeeding has not been reported in patients with PEP. Therefore, we investigated the safety and efficacy of early oral refeeding (ERF) compared to delayed refeeding (DRF) in patients with mild PEP through a prospective randomized controlled multicenter study.
Methods: Eligible patients were randomized to the ERF and DRF groups with a 1:1 ratio. In the ERF group, an oral diet was started 24 hours after PEP was diagnosed. In the DRF group, an oral diet was started after confirmation of restoring normal bowel sound, and abdominal pain decreasing below visual analog scale 2. The oral diet was started with sips of water and built up sequentially in the order of clear liquid diet - soft diet, considering patient tolerability. The oral refeeding was interrupted when the pain scale of the patient increased to VAS 5 points or more, or the patient refused diet due to abdominal pain or other reasons. After the interruption of refeeding, the diet was restarted after the amylase/lipase level decreased below the upper normal limit, the abdominal pain disappeared, and the bowel movement was restored. If the patient could tolerate more than 24 hours after completion of the diet build-up, it was determined that patient met the discharge criteria. The primary outcome was the hospitalization period for PEP, and secondary outcomes were the progression to severe AP, readmission rate (<30 days), mortality, and morbidity rate related to PEP.
Results: Between Feb. 2021 and Sep. 2022, 78 patients were enrolled in 9 referral centers and randomized to ERF (n=40) and DRF (n=38) groups (Figure 1). There was no significant difference between groups in baseline characteristics (age, sex, past history of acute pancreatitis, ERCP indications, smoking, alcohol, and other comorbidities) and procedural parameters (cannulation method, total procedure time, rate of difficult cannulation, pancreatic duct cannulation, and biliary stent insertion). The baseline severity of PEP was not different between groups. During refeeding, 4 patients in the ERF group and 3 patients in the DRF group were undergone interruption of refeeding (10% vs. 8%, p=0.745). The hospitalization period for PEP was significantly decreased in the ERF group compared to the DRF group (2.9 ± 1.6 vs. 3.9 ± 2.0 days, p=0.023, Figure 2). Severe AP, readmission (<30 days), mortality, and morbidity rate related to PEP did not occur in both groups.
Conclusion: Early oral refeeding significantly reduced hospital stays in patients with post-ERCP pancreatitis compared to delayed oral refeeding and did not increase PEP-related safety issues.

Figure 1. Study flow chart

Figure 2. The length of hospital days

Objective Endoluminal radiofrequency ablation (RFA) has been suggested a promising treatment modality for palliative treatment of cholangiocarcinoma (CCC) and pancreatic cancer (PC).
Methods In a randomized controlled manner, we compared endoluminal radiofrequency ablation plus stenting with stenting alone in patients with malignant biliary obstruction with survival as the primary outcome and stent patency as the secondary outcome.
Results A total of 161 patients with malignant biliary obstruction (85 with CCC and 76 with PC) were randomized [81 RFA + stent (44 CCC, 37 PC), 80 stent (41 CCC, 39 PC)]. The recruitment was terminated for futility after an interim analysis before enrolling the originally planned 280 patients. There was no difference in survival in patients with cholangiocarcinoma (median survival 10.5 months (95%CI 6.7-18.3) vs. 10.6 months (95%CI 9.0-24.8) and pancreatic cancer (median survival 6.4 months (95%CI 4.3-9.7) vs. 5.6 months (95% CI 5.6-11.3). Furthermore, no benefit was seen in stent patency in both CCC patients and PC patients. Complications occurred in 7 patients (8.6%) treated with RFA and 7 patients (8.8%) treated with stenting only (NS).
Conclusion In malignant biliary obstruction, endoluminal radiofrequency ablation in addition to stenting was not superior to stenting alone in prolonging survival or stent patency.

Introduction: Fatty pancreas is a poorly understood condition that has been associated with a higher risk of developing pancreatic cancer. SWE is a novel ultrasound-based imaging modality that evaluates tissue stiffness and fibrosis while overcoming the limitations of the traditional strain elastography. There is limited data on the use of SWE in the pancreas and its role in fatty pancreas. Therefore, the aim of the study is to investigate the utility of EUS-SWE to quantify fibrosis within the fatty pancreas.

Methods: This study is a prospective registry of consecutive patients who presented for standard-of-care EUS and consented to undergo EUS-SWE. For each patient, velocities of the S-wave (Vs=distance/time, m/s) were used to quantify tissue stiffness. Standardized SWE acquisition technique was formulated for the Head (HOP), Body (BOP) and Tail (TOP) of the pancreas. Each Vs measurement was accompanied by a reliability value (VsN%). Only VsN>50% were considered reliable and were included in the analysis. In this per-patient analysis, a patient was considered to have reliable measurements, if 5 (out of a maximum of 10) reliable Vs measurements were found per site. Overall reliability was compared across different sites using the chi-squared test. A univariate and multivariate logistic regression model was done to determine the predictors of fatty pancreas. Patient demographics, alcohol consumption, smoking history, and Vs measurements were included in the analysis.

Results: Of the 167 patients meeting the inclusion criteria, 23.8% were classified as having fatty pancreas on EUS by one of 5 experienced endoscopists. HOP was found to have the highest overall reliability with 141 patients (89.2%) followed by the BOP 128 patients (82.1%) and TOP 100 patients (68.5%, P<0.01). Only data from HOP (highest reliability) was used for univariate and multivariate logistic regression (Table 2). On univariate analysis, BMI (OR: 1.14 (95%CI:1.06-1.22), P<0.01) and SWE Vs measurements (OR: 2.74 (95%CI: 1.32-5.71), P<0.01) were associated with higher odds of fatty pancreas. Even after adjusting for BMI and patient demographics, SWE Vs measurement was independently associated with increased odds of fatty pancreas presentation (Table 2) and every 1 m/s increase in Vs reading was associated with 2.5 times the odds of having fatty pancreas (OR: 2.90 (95% CI: 1.13-7.4), P=0.04).

Conclusion: EUS-SWE has high reliability in measurement of stiffness, both in fatty and normal pancreas. This study reports a novel finding of higher Vs measurements in fatty pancreas and this is likely explained by a relative increase in stiffness by fat deposition which replaces the less stiffer acinar cells. If our findings are validated, this has the potential to be the only known ultrasound technique to quantitatively assess fatty pancreas.

Table 1: Comparison of Patient Characteristics Between Fatty and Normal Pancreas.

Table 1: Comparison of Patient Characteristics Between Fatty and Normal Pancreas.

Table 2: Univariate and Multivariate Logistic Regression Model for Fatty Pancreas Outcome.

Table 2: Univariate and Multivariate Logistic Regression Model for Fatty Pancreas Outcome.

Background and aims: Endoscopic retrograde cholangiopancreatography (ERCP) is an important interventional radiology procedure for the diagnosis and treatment of pancreatobiliary diseases. Although concerns about occupational hazards associated with radiation exposure during fluoroscopy are increasing, there has been little data regarding the amount of radiation medical staff are exposed to during ERCP and the effect of radioprotective lead glasses. Additionally, there have been no reports on the relationship between occupational radiation exposure to the lens of the eyes and radiation exposure to patients during actual ERCP in prospective multicenter studies. This study aimed to examine occupational radiation exposure during ERCP, its correlation with radiation exposure to patients, and the shielding effect of lead glasses.
Methods: This multicenter, prospective, observational study was performed in five hospitals for three consecutive months (October 2020 to December 2020). We examined occupational radiation exposure to the lens of the eyes during ERCP and the effects of lead glasses in cases where eye dosimeters (attached inside and outside the lead glasses) and glass badges over lead aprons were used. We also collected data on radiation exposure to patients (air kerma at the patient entrance reference point (K_a,r) (mGy), kerma-area product (P_KA) (Gycm²), fluoroscopy time (FT) (min) and radiation dose rate (RDR) (mGy/min)).
Results: In total, 631 ERCPs were measured dosimetrically. For radiation exposure to patients, the median Ka,r was 49.6 mGy, the median P_KA was 13.5 Gycm², the median FT was 10.9 min, and the median RDR was 5.0 mGy/min. The median estimated annual radiation dose to the lens of the eyes was 3.7 mSv in operators, 2.2 mSv in assistants, and 2.4 mSv in nurses, respectively. While the median difference from the radiation dose measured by the eye dosimeter to the measurement results of the glass badge was comparatively small (-2.2%), it largely differed in assistants (-51.1%) and nurses (-36.4%). Strong, positive correlations were shown between occupational lens exposure and radiation exposure to patients (Ka,r, P_KA, and FT) in operators, assistants, and nurses. The shielding rates of the lead glasses were approximately 50% (operators 44.6%; assistants 66.3%; nurses 51.7%).
Conclusions: This multicenter prospective study showed positive and strong correlations between occupational radiation exposure to the lens of the eyes and radiation exposure to patients, as well as the actual radiation exposure to the lens of the eyes of medical staff during ERCP. Although the use of eye dosimeters attached to lead glasses is recommended for measuring radiation exposure accurately, the values of radiation exposure to patients can help in estimating radiation exposure to the lens of the eyes of medical staff because of their strong correlation.

Mamoru Takenaka

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