Introduction

Fistula formation in the gastrointestinal (GI) tract associated with walled-off necrosis (WON) may complicate the clinical course of patients with acute pancreatitis. Identifying prognostic factors for this complication would help optimise the treatment algorithm for patients with WON and improve clinical outcomes.

Aims & Methods

In our multicentre cohort of 76 patients receiving endoscopic ultrasound-guided pancreatic fluid drainage (EUS-PFD) for WON between 2010 and 2023, we identified 27 patients with a GI tract fistula and examined prognostic factors for the development of this complication. We additionally examined factors for a severe GI fistula defined as a requirement of surgical management or death from uncontrollable infection presumably due to the fistula.

Results

Among the 27 cases with a GI fistula, there were 12, 9, and 5 cases with a fistula in the colon, duodenum, and small intestine, respectively. No statistically significant differences were noted between the groups with and without a GI fistula in terms of age (median; 65 vs. 69 years, respectively), female sex (19% vs. 27%, respectively), aetiology of pancreatitis (alcohol / ERCP-related / gallstone, 28%/28%/20% vs. 28%/20%/26%, respectively), maximum WON diameter (14 cm vs. 14.5 cm, respectively), or ascites (26% vs. 35%). WON extension to the paracolic gutter or the pelvic cavity was associated with a higher risk of a GI fistula with odds ratios of 3.3 (95% confidence interval, 1.2-8.8) and 5.6 (95% confidence interval, 1.9-16.7), respectively. Fistulas occurring in the colon were more likely to be severe compared to those occurring in the other sites. Compared to patients with non-severe or no GI fistula, patients with a severe GI fistula were more likely to undergo a longer hospitalisation with medians of 165 days vs. 57 days (P < 0.01). In an investigation of treatment outcomes between colonic and non-colonic fistulas, non-colonic fistulas were successfully managed by EUS-PFD and supportive care in all cases compared to 67% in colonic fistulas (P = 0.03). All four cases with unsuccessful endoscopic management of a colonic fistula were characterised by a fistula size of > 5 mm or penetrating to the bladder. Among the four cases, three cases required surgical resection of the colon, and one case died of uncontrollable infection despite an attempt of endoscopic fistula closure with an over-the-scope clip.

Conclusion

In this multicentre cohort study, WON extending to the paracolic gutter or pelvic cavity was a risk factor for the incidence of a GI fistula, and colonic fistulas were associated with unfavourable clinical outcomes. A substantial proportion of endoscopic treatment failures were noted in patients with a colonic fistula, suggesting the necessity of considering treatment strategies for this subpopulation (including the timing of salvage surgery).

Disclosure

H.I. declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; and honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical.
Y.N. declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. The other authors declare no conflicts of interest related to this article.

Introduction

Despite EUS-guided drainage (EUS-FCD) is the preferred modality for management of peripancreatic fluid collections (PFCs), factors predicting the need for step-up to additional procedures (including radiology, surgery or additional endoscopies) are retrospectively explored in studies restricted to Lumen Apposing Metal Stents (LAMS) or excluding pseudocysts and post-surgical collections, which might require a step-up as well.

Aims & Methods

All consecutive candidates to EUS-FCD with either LAMS or Double-pigtail Plastic Stents (DPPS) between 2020-2023 were included in a Prospective Registry of Therapeutic EUS (PROTECT). The role of baseline clinical and morphological factors, including the Quadrant / Necrosis / Infection (QNI) score, in predicting the need for any step-up to additional procedures was evaluated by stepwise logistic regression.

Results

Twenty-three post-surgical PFCs, 19 pseudocysts and 18 walled-off necrosis [WOPN]) were included, 42% treated with LAMS and 58% with DPPS based on morphology. Clinical success was 92.9%, but 38% of patients required a step-up to necrosectomy (26.7%) or additional procedures. Patients requiring step-up versus those sufficing drainage had a higher number of quadrants involved (OR=3.6 [1.5-8.4]), a more frequent paracolic extension (OR=6 [1.4-26]), a higher necrosis content (>30%, OR=7.2 [1.8-28.4] ; >60% OR=25.2 [4.2-153]) and were in the high-risk group according to the QNI score, with no difference in the diameter and rate of superinfection. At multivariate analysis, being in the high-risk QNI group was the only independent predictor of step-up (OR=9.8 [2.9-32.9]). The score however was not able to stratify in analyses restricted to WOPN only or LAMS only. High-risk QNI patients presented also a longer hospital stay (17.5 [8-45] vs 4 [2-6.5], p=0,001), without any difference in ICU stay and nutritional support.

Conclusion

In this prospective series of consecutive non-selective PFCs undergoing EUS-FCD, QNI score was the only independent predictor of any need for step-up to additional procedures, and strongly correlated to the EUS-FCD allocation to LAMS versus DPPS, unravelling a potential additional utility.

Disclosure

GV reports travel grants from Pentax Medical, Boston Scientific and Euromedical, and lecture fees by Boston Scientific.
All the other authors ​declare no conflict of interest.

Introduction

Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.

Aims & Methods

We aimed to provide a detailed clinical and laboratory characterization of a large prospective NPHL patient cohort and assess parameters determining disease outcomes.
A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.

Results

A total of 808 patients [male, n = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% vs 5.1%, P < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, P < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.

Conclusion

NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.

Introduction

Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10%. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant collagen deposition in the tumor stroma. However, the precise impact of this phenomenon on PDAC remains unclear.

Aims & Methods

This study aimed to clarify the interactive relationship between tumor stromal collagen and its molecular characteristics, immune characteristics, and tumor progression in human PDAC. The goal is to elucidate the mechanism of fibrosis in PDAC. A comprehensive examination was performed using a molecular pathological epidemiology database on 169 cases with resected PDAC.
Among 234 patients who underwent pancreatectomy surgery between April 2008 and March 2017 at Kobe University, 169 conventional PDAC patients were analyzed. Patients with special type pancreatic cancers, with stageⅣ PDAC, who underwent preoperative radiation, and without available FFPE samples were excluded. The following information was collected retrospectively about these patients: age, gender, body mass index, family history, blood test results, surgical pathology specimen, and treatment course.
We quantified the amount of tumor stromal collagen by digitally processing EVG-stained whole-section slides. Gene alterations (KRAS, TP53, CKDN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and marker of cancer-associated fibroblasts such as αSMA were evaluated by immunohistochemistry, next-generation sequencing, and droplet digital PCR.

Results

Multivariate logistic regression analysis revealed that low stromal collagen levels were linked to poor differentiation (P=0.008) and CDKN2A/p16 alteration (P=0.03) of PDAC. Additionally, low stromal collagen levels were found to be an independent poor prognostic factor. The overall survival of such patients was significantly shorter (22.1 months vs. 38.0 months, P=0.001).
Regarding those who underwent chemotherapy, low amounts of stromal collagen were linked to poor prognosis in the S-1 (P= 0.005) and gemcitabine (P= 0.007) treatment groups. Furthermore, they were linked to low levels of CD4+ tumor-infiltrating lymphocytes (TILs) (P=0.046), CD8+ TILs (P=0.09), and tertiary lymphoid structures (P=0.001).
The mechanism by which fibrosis is associated with prognosis is not well-defined. The components of tumor microenvironment are diverse, including cancer cells, fibroblasts, immunocompetent cells, and extracellular matrix. Thus, we explored comprehensively the factors and mechanisms that define fibrosis with Spatial Transcriptome. Gene expression analysis was performed using two sets of four cases with different amounts of stromal collagen. The gene expression could be classified into 7 clusters. The cancer cells in the low amounts group consisted of one cluster and those in the high amounts group consisted of two clusters on the hand. Enrichment analysis on the distinctive cluster in the high amounts group revealed that it was genes that activated the TGFβ pathway.

Conclusion

The amount of tumor stromal collagen varies in tumor characteristics, prognosis, and response to postoperative chemotherapy in PDAC, and may affect the modulation of the tumor immune microenvironment. We found that there is a group of genes that are characteristically expressed in PDAC with high amounts of stromal collagen and a good prognosis. Further studies will be conducted to elucidate the mechanisms that regulate fibrosis.

Introduction

Pain in acute pancreatitis is the symptom to be treated urgently. There are currently no recommendations for analgesic management. Intravenous lidocaine has both analgesic and anti-inflammatory effects. Its use has never been evaluated for analgesia in acute pancreatitis. The aim of our study was therefore to evaluate the efficacy and safety of intravenous lidocaine in the management of acute pancreatitis resistant to level I and II analgesics.

Aims & Methods

We conducted a retrospective, monocentric study between January 2015 and December 2021. Patients visiting the emergency department for proven acute pancreatitis and presenting with pain resistant to group I and II analgesics, hospitalized in the hepato-gastroenterology department and treated with intravenous lidocaine, were included. Pain was assessed by retrospective collection of numerical pain scales (NPS) at the emergency department, and at each analgesic re-evaluation. Treatment efficacy was defined as the absence of need for a Level III analgesic (opioids).

Results

154 patients, hospitalized in our gastroenterology unit for acute pancreatitis and presenting with pain refractory to level I and II analgesics treated with intravenous lidocaine were included. Patients were predominantly male, with a median age of 48.5 years [37.0; 58.0]. The main etiology of acute pancreatitis was ethylic in 36% of cases. Acute necrotizing pancreatitis was present in 69% of patients. 44/154 patients received a bolus of opioid morphine in the emergency department before the administration of lidocaine. Lidocaine was prescribed in a continuous way at the dose of 2g/24h (intravenous administration with electric syringe). The median NPS before prescription of lidocaine was 8.0 [7.00; 9.00]. Lidocaine treatment was effective in 88.7% of patients (136/154). 1.3% of patients experienced lidocaine-related adverse events such as skin rash and dysgeusia. In univariate analysis, patients requiring intensive care or developing an acute respiratory distress syndrome were significantly more likely to fail lidocaine (respectively OR = 5.83; CI [1.69; 20.06]; p=0.01 and OR = 4.23; CI [1.44; 12.43]; p=0.009).

Conclusion

Intravenous lidocaine administration appears to be effective and safe for pain control in 89% of patients failing to level I and II analgesia. Further prospective studies are needed to confirm these results.
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Introduction

While understanding the cause is pivotal for managing acute pancreatitis (AP), there is currently no established protocol for determining its aetiology. Ongoing research aims to validate diagnostic protocols and integrate advanced tests for cases of idiopathic acute pancreatitis (IAP). This study evaluated current international opinion about diagnosis and follow-up of IAP.

Aims & Methods

An international survey was conducted through an online survey platform; the link was shared through social media, e-mails and conference presentations. Responses were collected anonymously. The 37 questions were developed by an international multidisciplinary team, part of a Pancreas2000 collaborative project.

Results

Respondents (n=247) were from over 35 countries; 39% of them had over 10 years of clinical experience; 73% were working in tertiary referral centres; 56% were gastroenterologists, 34% surgeons. An equal number of respondents (n=85, 34%) chose magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) as the first test ideally performed in case of no suspected aetiology for AP after basic tests. When both investigations were available in the respondents’ centre, 44% chose other tests, 30% MRCP and 27% EUS. If there is no evidence of biliary aetiology, 79% of respondents would not perform cholecystectomy; the rest would choose recurrent AP and a history of elevated liver enzymes as main indications. No correlation was found when comparing tertiary and non-tertiary centres in performing cholecystectomies, similarly when comparing centres with or without EUS availability. Most respondents (90%) followed up on moderate and severe AP cases without an aetiology at index admission; 53% of centres followed up on all the IAP cases after first discharge. The follow-up was mostly done by gastroenterologists (62%); 33% of specialists would conduct a follow-up visit every 6 months, while 17% wouldn’t recommend follow-up visits.

Conclusion

This international survey highlights the lack of standardisation for diagnosis and follow-up of IAP. Although MRCP and EUS were ideally chosen as first options in IAP diagnosis, respondents chose other investigations in their practice even when both were available. Only half of the centres schedule visits, showing a lack of consensus regarding follow-up. There is a need for international standardisation for diagnosis and follow-up of IAP.