Introduction

There has been no consensus on the appropriate timing of endoscopic ultrasound (EUS)-guided interventions for pancreatic fluid collections (PFCs) secondary to acute pancreatitis.

Aims & Methods

Among 454 patients receiving EUS-guided treatment for PFCs at 11 centers in Japan, we included 315 patients with available data on the onset of acute pancreatitis (222 with WON and 93 with pseudocysts). We categorized the timing of treatment initiation as early (< 4 weeks of the onset of acute pancreatitis, n = 75) and delayed (≥ 4 weeks, n = 240) and examined their association with clinical outcomes. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using the logistic regression model adjusting for potential confounders.

Results

Patients receiving early interventions were more likely to have higher levels of inflammatory markers (white blood cell count and C-reactive protein) and a smaller PFC size. The delayed intervention group was characterized by higher rates of full capsulation of the lesion and the requirement for necrosectomy. Compared to early interventions, delayed interventions were associated with higher rates of technical success (98.7% vs. 94.6%; adjusted OR, 4.431; 95% CI, 0.969-20.26; P = 0.058) and clinical success (84.5% vs. 70.6%, adjusted OR, 2.277; 95% CI, 1.239-4.183; P = 0.010). The total rates of procedure-related AEs did not differ by timing. However, patients receiving early interventions were more likely to undergo moderate or severe AEs (14.6% vs. 6.2%, P = 0.029) and in-hospital deaths (18.6% vs. 7.5%, P = 0.002).

Conclusion

Despite poorer conditions of patients receiving early interventions, this population was characterized by lower rates of technical and clinical successes with a higher mortality rate. Therefore, therapeutic indications for PFCs should be considered prudently in the early phase of acute pancreatitis.

References

1) Banks PA, Bollen TL, Dervenis C et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013; 62: 102-111
2) Baron TH, DiMaio CJ, Wang AY et al. American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis. Gastroenterology 2020; 158: 67-75
3) Oblizajek N, Takahashi N, Agayeva S et al. Outcomes of early endoscopic intervention for pancreatic necrotic collections: a matched case-control study. Gastrointestinal endoscopy 2020; 91: 1303-1309

Disclosure

Y.N. received research grants from Boston Scientific Japan, HOYA Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, Olympus Corporation. H.I. received research grants from Boston Scientific Japan, Fujifilm Corporation, Fujifilm Health Care Corporation, Gadelius Medical KK, Zeon Medical Inc., and honoraria from Boston Scientific Japan, Fujifilm Corporation, Taewoong Medical Devices, Olympus Corporation, Century Medical,Inc. and Cook Medical Japan G.K. Y.I. received honoraria from Gadelius Medical KK and Medicos Hirata.

Introduction

PNET is an important determinant of survival in MEN1 patients and the most important cause of MEN1-related death. Early identification of pNETs in MEN1 is important since these represent a common cause of morbidity and mortality of the syndrome. Prognosis is associated with tumour size. Many pNETs are small subcentimetre lesions and only become symptomatic when the tumour is large. Conventional radiology is usually suboptimal in detecting small tumours (< 2cm), thus missing the window to remove them at an earlier stage. We aim to compare EUS detection of pNETs in patients with confirmed MEN1 compared to cross-sectional imaging including CT and/or MRI pancreas and assess the incremental benefit of EUS.

Aims & Methods

Over a span of 7 years, a total of 20 patients with clinically confirmed MEN1 had surveillance of pNET performed with EUS, CT/MRI and biochemical screening. Data were retrospectively retrieved from the hospital electronic records database. EUS and CT/MRI done within 3-6 months of each other were compared to minimize discrepancy in findings due to pNET size progression and new lesions over time. Statistical analysis was performed using SPSS v20 on the size and number of pNET detection by EUS and CT/MRI using the Wilcoxon Signed Rank Test and McNemar Chi-square.

Results

A total of 28 EUS procedures and an equal number of cross sectional imaging (CT/MRI) were performed. pNETs were identified in 95% of all 20 MEN1 cases. Overall median pNET size was 7.1mm on EUS and 14.5mm on CT/MRI (p=0.007). Mean value for smallest PNETs detected by EUS was 4.6mm and 12.7mm on CT/MRI (p=0.001). EUS detected more pancreatic lesions/pNETs compared to CT/MRI (p<0.001) in 25 of the 28 procedures (89.3% more). The remaining 3 procedures showed equal numbers of pNETs detection by both modalities. The interquartile range (IQR) for smallest pNET detected by EUS was 3.0-5.0mm while IQR for CT/MRI lies between 8.3mm-14.8mm. EUS detected all 100% cases of pNETs in our series of MEN1 compared to CT/MRI imaging alone which detected 57.9% cases (p=0.008). 14 of 20 patients had FNA performed with a positive yield of 85.7%. In 50% of patients, pNET measured ≤10 mm. 45% of patients underwent surgery for pNETs while the rest had surveillance.

Conclusion

In MEN1 patients, CT/MRI underestimated the presence of pancreatic lesions/pNETs in 42.1% compared to EUS (p=0.008) and was not able to identify pNETs < 8mm in all but one case.
EUS offers higher sensitivity than cross sectional imaging (CT/MRI) in terms of detecting the number of positive pNET cases as well as a greater number of pancreatic lesions especially subcentimetre lesions in MEN1. EUS should be considered a standard tool in the algorithm for MEN1 workup, instead of an adjunct reserved for diagnostic dilemmas.

References

NCCN Guidelines 2015 version 1.2015 Neuroendocrine Tumours.

Introduction

Mast cells play an important role in the human innate immune system, however, their role in liver disease is not fully understood. Histamine is a key component of mast cells granules and plasma histamine levels have been found to be increased in patients undergoing liver transplantation. However, their relationship with circulatory function and outcome have yet to be evaluated.

Aims & Methods

Two hundred fifty-one patients (pts) who underwent hepatic venous pressure gradient (HVPG) measurement (= baseline, BL) from 04/2017 until 03/2020 as part of the prospective Vienna Cirrhosis Study (VICIS) and had ACLD (as defined by the presence of portal hypertension (HVPG ≥6mmHg) and/or a liver stiffness measurement ≥10kPa, as assessed by vibration-controlled transient elastography) were included.

Results

Alcohol-related liver disease (102 pts, 40.6%) and viral hepatitis (51 pts, 20.3%) were the most common etiologies. Median HVPG was 17 mmHg (IQR 12-21) and 207 (82.5%) pts had clinically significant portal hypertension, i.e., an HVPG ≥10mmHg. About half of the pts were decompensated at BL (135 pts, 53.8%). Regarding Child-Turcotte Pugh (CTP) stages, 142 pts (56.6%) were stage A, 84 pts (33.5%) stage B, and 25 pts (10.0%) stage C. Sixty-seven pts (26.7%) had a model for end-stage liver disease (MELD) score ≥15.
The median plasma histamine concentration was 8.5nmol/L (IQR 6.3-11.5) and histamine levels above the upper limits of normal limit (i.e., 9.9nmol/L) were found in 37.1% of pts. Histamine concentrations did not differ significantly across CTP, MELD, or HVPG strata, but showed weak positive correlations with markers of circulatory dysfunction (i.e., plasma renin and serum sodium).
During a median follow-up of 28.9 month, acute-on-chronic liver failure (ACLF) and liver-related death were observed in 69 and 52 pts, respectively. Interestingly, plasma histamine levels were predictive of ACLF or liver-related death (univariate Cox proportional hazards model; hazard ratio [HR]: 1.023 per nmol/L; 95% confidence interval [95%CI]: 1.007-1.039; p = 0.004 and overall mortality (HR: 1.021; 95%CI: 1.005-1.038; p = 0.010). When adjusting for age, sex, CRP, HVPG, as well as either for MELD, decompensation, and serum albumin or for CTP and serum sodium, histamine levels remained associated with ACLF or liver-related death: CTP-based model: HR: 1.033; 95%CI 1.014-1.053; p < 0.001; MELD-based model: HR: 1.030; 95%CI: 1.010-1.050, p = 0.003.

Conclusion

We found that high plasma levels of histamine correlated with markers of circulatory dysfunction and were associated with increased risks of ACLF and liver-related death. Further studies investigating the underlying mechanism (i.e., mast cell activation vs. decreased degradation) as well as the role of histamine and related therapeutic strategies in hyperdynamic circulation and ACLF development are warranted.