Clinical Case Summary

A 54-year-old man was referred to a Gastroenterology appointment due to weight loss and abnormal pancreatic findings on a CT scan, which revealed massive pancreatic enlargement. He had no relevant medical history. Endoscopic ultrasound demonstrated a globular pancreas with a hypoechoic but highly heterogeneous echotexture, multiple subcentimetric nodular formations and numerous millimetric hyperechoic foci, consistent with calcifications. Chromogranin A level was elevated at 143.2 ng/mL.
A 22G fine-needle aspiration of the pancreatic parenchyma was performed, but the result was inconclusive. Subsequently, PET/CT with 68Ga-peptides revealed a focal area of markedly increased uptake in the pancreatic tail (SUV max 47.8), highly suggestive of a neuroendocrine neoplasm, with increased radiotracer uptake throughout the pancreas. As a result, a percutaneous biopsy of the neoplasm and surrounding parenchyma (tail and body) was performed, confirming a well-differentiated (G1) pancreatic neuroendocrine tumor with amyloid stroma. Treatment was initiated with octreotide, later transitioned to lanreotide.
The patient underwent genetic evaluation, which revealed likely pathogenic variants c.1176+1_1176+7del p.? and c.361T>C p.(Cys121Arg) in the GCGR gene (heterozygous), confirming a diagnosis of Mahvash disease.
Two years later, during follow-up, abnormal liver function tests prompted abdominal magnetic resonance imaging, revealing liver nodules with characteristics of hypervascular metastases and signs of portal hypertension. An upper endoscopy was performed, revealing large esophageal varices with red spots, which were treated with two prophylactic elastic band ligations.
This case illustrates the development of portal hypertension arising from an extremely rare genetic disorder, with only about 15 confirmed cases of Mahvash disease reported to date. It is comprehensively documented through CT, PET imaging, histology, endoscopic ultrasound and upper endoscopy iconography.

References

- Yu, Run. “Plea to radiologists: Please consider Mahvash disease when encountering an enlarged pancreas.” World journal of radiology vol. 16,8 (2024): 371-374. doi:10.4329/wjr.v16.i8.371
- Robbins, Justin et al. “Liver Transplantation in a Woman with Mahvash Disease.” The New England journal of medicine vol. 389,21 (2023): 1972-1978. doi:10.1056/NEJMoa2303226

Clinical Case Summary

An 82-year-old man with Child B alcoholic cirrhosis, complicated by portal hypertension, underwent surveillance upper digestive endoscopy (UDE), revealing large esophageal varices and a 20 mm exophytic lesion, 40 cm from the dental arch, with an infiltrative and ulcerated appearance. Biopsies were inconclusive. Endoscopic ultrasound identified a heterogeneous, amorphous lesion with poorly defined borders and disruption of all wall layers, complicated by numerous large varices, preventing biopsy due to hemorrhagic risk. Computed tomography revealed parietal thickening in the distal esophagus and multiple varices, complicating lesion delineation. An oncology consultation recommended clinical surveillance, considering the patient's age, comorbidities, indeterminate nature of the esophageal lesion, and low suspicion for adenocarcinoma on ultrasound. One year later, surveillance UDE showed regression of the lesion.Histological samples were reviewed, revealing changes consistent with pyogenic granuloma. Pyogenic granuloma is a rapidly growing capillary hemangioma that may occur within the lumen of a pre-existing vessel (intravascular variant). The case is supported by appropriate iconography.

This case is presented with imaging, highlighting the challenge due to the macroscopic appearance suggestive of a neoplastic lesion and the pyogenic granuloma's growth within esophageal varices, limiting diagnostic and therapeutic management.

References

Clinical Case Summary

Background: Endoscopic ultrasound (EUS)-guided cystogastrostomy with lumen-apposing metal stents (LAMS) is a widely accepted treatment for symptomatic pancreatic pseudocysts, particularly in cases of walled-off necrosis (WON). While the procedure is generally safe, delayed bleeding can occur. This report presents a novel approach to managing massive upper gastrointestinal bleeding following LAMS placement when interventional radiology (IR) embolization is not feasible.
Case presentation: A 51-year-old male with a history of pancreatitis and a large pancreatic pseudocyst underwent successful EUS-guided placement of an Axios stent. The patient was discharged on the second day of the procedure with no adverse events. Three days later, the patient developed significant melena, pallor, and a dramatic drop in hemoglobin levels, necessitating urgent blood transfusions. Diagnostic upper endoscopy revealed active pulsatile bleeding from the cyst wall behind the stent edge, which is inaccessible to conventional endoscopic methods. Two attempts of angiography by two different IR consultants failed to locate the bleeding source.
Given the critical situation and after resuscitation with IV blood transfusion, a multidisciplinary team proposed a novel technique: injection of Purastat, a hemostatic agent, into the cyst through the stent, followed by stent removal and additional application of glue over the cyst orifice. This approach successfully controlled the bleeding, stabilized the patient’s condition, and eliminated the need for surgery. Follow-up imaging revealed a small splenic artery aneurysm without active bleeding.
Conclusion: This case highlights the potential of Purastat as an effective tool for managing life-threatening gastrointestinal bleeding following LAMS placement. The successful use of this technique in sealing the cyst and stopping the bleeding suggests it could be a definitive management option in similar cases.

References

1. Shamah S, et al. Delayed bleeding after lumen-apposing metal stent placement for pancreatic fluid collections: Incidence, risk factors, and management. *Endoscopy International Open*. 2023;11(2):E158-E163.
2. Varadarajulu S, et al. Hemostasis in gastrointestinal endoscopy: Emerging techniques and devices. *Gastrointestinal Endoscopy Clinics of North America*. 2022;32(3):421-439.

Introduction

Phase Angle (PA) represents a useful bioimpedance analysis-assessable marker of sarcopenia, accurately predicting liver-related hospitalizations in advanced chronic liver disease (ACLD), correlating with C-reactive protein levels. Clinically significant portal hypertension (CSPH) and systemic inflammation constitute the main hepatic decompensation drivers. A relevant proportion of Metabolic dysfunction-associated steatotic liver disease (MASLD) patients present sarcopenia (configuring the paradox of “sarcopenic obesity”), as well as compensated ACLD (cACLD)-MASLD individuals more rapidly progress to decompensation (dACLD) rather than other etiologies. However, the clinical applications of PA have never been specifically investigated in the setting of MASLD.

Aims & Methods

Considering the background, in MASLD, we primarily aimed to evaluate the trend of PA values across the different liver disease progression stages, investigating the relationship with the hepatic decompensation drivers; in dACLD-MASLD, we aimed to estimate the accuracy of the novel PA/C-reactive protein (CRP) index (PAC-I) in predicting 3-month further liver-related events (LREs)-determining hospitalizations.
In this observational study, between December 2023 and January 2025, MASLD patients were consecutively enrolled and stratified according to current LSM and eventual previous LREs in < F3 fibrosis (AF) (n.50), cACLD (n.50), and dACLD (n.50) patients. At baseline, anthropometrical, biochemical, nutritional, and clinical data [including the endoscopic assessment of CSPH and the relative severity (F1, F2, F3) of esophageal varices (OEVs)] were collected. Bioimpedance analysis was adopted to assess body composition parameters. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia (EGWSOP2) criteria. MASLD-dACLD patients were followed up, and further acute decompensation (AD)-LREs-determining hospitalizations [severe ascites, severe hepatic encephalopathy (HE), OEV bleeding, and any acute bacterial infections] in the subsequent 3 months were recorded.

Results

In MASLD patients, PA (°) values inversely correlated with LSM [R: -0.711; p<0.0001], progressively decreasing according to the worsening of liver disease stages, emerging as statistically significantly lower in dACLD compared with cACLD individuals (p<0.0001). In dACLD patients, PA inversely correlated with CRP levels [R: -0.945; p:0.001]. Focusing on CSPH, PA values were significantly lower in > F2-OEV-affected individuals (p<0.0001). Multivariate analysis revealed CSPH (aHR 1.221, p<0.0001), CRP (aHR: 1.112, p:0.002), and PA (aHR: 1.178, p:0.003) as the variables significantly associated with 3-month further LREs’ occurrence in dACLD patients.
ROCy analysis revealed an elevated accuracy and superiority compared to PA alone (AUC PA:0.717; AUC PAC-I: 0.893; p:0.003) of PAC-I in predicting 3-month further LREs’ occurrence, identifying PAC-I < 2.35 as the best cut-off. Consistently, dACLD patients showing baseline PAC-I < 2.35 presented a higher risk [HR: 2.287, p: 0.032] of further LREs.

Conclusion

In MASLD, PA correlates with the main driver of progression, and the PAC-I represents a useful noninvasive tool in predicting short-term liver-related hospitalizations in dACLD patients.

References

1. Espirito Santo Silva DD, Waitzberg DL, Passos de Jesus R, Oliveira LPM, Torrinhas RS, Belarmino G. Phase angle as a marker for sarcopenia in cirrhosis. Clin Nutr ESPEN. 2019 Aug;32:56-60. doi: 10.1016/j.clnesp.2019.05.003. Epub 2019 May 31. PMID: 31221291.
2. Saueressig C, Glasenapp JH, Luft VC, Alves FD, Ferreira PK, Hammes TO, Dall'Alba V. Phase Angle Is an Independent Predictor of 6-Month Mortality in Patients With Decompensated Cirrhosis: A Prospective Cohort Study. Nutr Clin Pract. 2020 Dec;35(6):1061-1069. doi: 10.1002/ncp.10584. Epub 2020 Oct 15. PMID: 33058222.

Introduction

It is recognised that large common bile duct (CBD) stones present a significant challenge in endoscopic practice. A key performance indicator of >80% clearance at the initial ERCP has been recommended to standardise quality of care. Standard techniques such as sphincterotomy +/- balloon sphincteroplasty are usually sufficient; however, in difficult cases, plastic stents are frequently placed to maintain biliary drainage, with elective repeat ERCP planned. When clearance remains unsuccessful, options such as mechanical lithotripsy or cholangioscopy may be employed, though these are often limited to tertiary care centres. Fully covered self-expanding metal stents (FCSEMS) have been proposed as a novel strategy to remodel the distal CBD and facilitate stone retrieval at subsequent procedures. While this approach is not currently included in formal UK guidelines, its use is expanding in complex cases. We report our early experience comparing plastic stents alone with a combination of fully covered metal stents and coaxial plastic stents in a secondary care setting.

Aims & Methods

This was a retrospective observational study conducted at a large secondary care NHS trust. We included patients undergoing ERCP between 2019 and 2024 in whom complete stone clearance could not be achieved at the initial procedure and a stent was placed. Only patients with confirmed choledocholithiasis and naïve papillae at first ERCP were included. All patients had large CBD stones, defined as stones greater than 10 mm in diameter. Patients were categorised according to whether a plastic stent alone or a fully covered metal stent with coaxial plastic stent was used at the index procedure. A 7Fr pigtail plastic stent was used in all cases; for the FCSEMS group, a fully covered metal stent was inserted with a plastic stent placed through it. Data were collected from endoscopy records and electronic patient notes. Outcomes assessed included complete stone clearance at second ERCP, need for mechanical lithotripsy, number of ERCP procedures, and referral to tertiary care for cholangioscopy. Fisher’s exact test and unpaired t-tests were used for statistical analysis.

Results

A total of 63 patients were included, with 46 in the plastic stent group and 17 in the FCSEMS group. Complete stone clearance for large stones (>10 mm) at second ERCP was achieved in 63.0% of patients in the plastic group compared with 76.5% in the FCSEMS group (p=0.380). Mechanical lithotripsy was required in 8.7% of plastic stent cases and 5.9% of FCSEMS cases (p=1.000). Referral to tertiary care for cholangioscopy occurred in 30.4% of the plastic group and 11.8% of the FCSEMS group (p=0.195). The mean number of ERCPs per patient was similar between groups, with an average of 2.50 procedures in the plastic group and 2.41 in the FCSEMS group (p=0.601).

Conclusion

The use of fully covered metal stents with coaxial plastic stents was associated with promising trends, including higher rates of complete stone clearance for large CBD stones and fewer referrals to tertiary centres. Although these findings did not reach statistical significance, they suggest a clinically relevant benefit that merits further investigation. The higher observed clearance rate and reduced need for cholangioscopy may support FCSEMS as a valuable adjunct in managing difficult bile duct stones. These results should be interpreted cautiously given the small size of our dataset, but they provide an encouraging basis for future prospective studies aimed at optimising CBD stone management and potentially reducing the need for tertiary care referral.

Disclosure

Nothing to disclose

Introduction

Although patients with acute-on-chronic liver failure (ACLF) often demonstrate preserved thrombin generation (TG), they concurrently display hypocoagulable profiles on rotational thromboelastometry (ROTEM) [1]. The extent to which these findings explain the increased bleeding risk in acutely ill cirrhotic patients remains unclear [1–5]. Moreover, most studies do not distinguish between portal hypertensive (PH) and non-PH bleeding, complicating accurate estimation of NPH bleeding prevalence.

Aims & Methods

This is a case-control study, comparing haemostatic profiles of acute decompensation (AD) and ACLF (=cases) to stable cirrhosis (SC) (=controls). Coagulation profiles were evaluated including INR, aPTT, PT, fibrinogen, coagulation factors and inhibitors and advanced global haemostatic tests (ROTEM, TG assay (TGA) ± thrombomodulin (TM)). Secondary objectives focused on identifying associations between coagulation parameters and NPH bleeding and thrombotic events.

Results

A total of 215 patients were included (SC: 122; AD: 53; ACLF: 40). The median Child-Pugh (CP) and MELD-Na scores increased progressively from SC to AD to ACLF (P< 0.001). NPH bleeding occurred in 8,4% (n=18), with higher rates in ACLF (30,8%, P<0,001) and AD (18.9%, P=0.011) than in SC (5.7%). Thrombotic events were observed in 7.0% (n=15).
TGA without TM revealed that ACLF patients had significantly shorter lag time compared to SC, shorter time to peak, reduced peak height and endogenous thrombin potential (ETP) compared to SC/AD; though TM normalized these effects. ETP inhibition by TM was reduced significantly across the three groups. ROTEM parameters showed marked hypocoagulable features in ACLF vs SC/AD, while AD and SC were comparable. Hypocoagulability (≥5 abnormal ROTEM parameters out of 6 parameters) was present in 1.8% of SC, 8.3% of AD, and 22.2% of ACLF patients (P<0.001 for SC vs ACLF); hypercoagulability was rare (2.8% in ACLF). INR and aPTT were significantly prolonged and FVIII elevated, while fibrinogen, PT, and pro- and anticoagulants were reduced in AD/ACLF compared to SC. ROTEM and TGA parameters correlated significantly with MELD-Na and CP scores (P<0,001).
Patients with NPH bleeding had higher CP and MELD-Na scores (P<0,001 and P=0,006), and a greater prevalence of AD (33,3%) and ACLF (38,9%) compared to non-bleeders (22,8% AD; 16,1% ACLF). Hypocoagulability on ROTEM was more frequent among bleeders (31.3% vs 4.5% in non-bleeders, P=0.002). Bleeders also showed greater impairment in INR, aPTT, PT, and most coagulation factors (except FVIII and PS). Multivariate analysis identified ROTEM-defined hypocoagulability as an independent risk factor for NPH bleeding (OR 12.93, 95% CI: 1.13–150.28, P=0.041). No significant differences in coagulation parameters were observed between patients with and without thrombotic complications.

Conclusion

TG demonstrated accelerated initiation and reduced thrombin potential in ACLF vs SC/AD, though TM normalized these effects. ROTEM demonstrated pronounced hypocoagulability in AD/ACLF vs SC. These coagulation abnormalities are paralleling their advanced liver dysfunction.
NPH bleeding events clustered in AD/ACLF cohorts and were associated with ROTEM-defined hypocoagulability. The convergence of ROTEM hypocoagulability as an independent risk factor for NPH bleeding and its prominence in acutely ill cirrhotic patients underscores the heightened NPH bleeding prevalence and ROTEM detected coagulation dysfunction in this patient population.

References

1. Campello E, Zanetto A, Bulato C, Maggiolo S, Spiezia L, Russo FP, et al. Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure. Liver International. 2021 Oct 16;41(10):2455–66.
2. Drolz A, Horvatits T, Roedl K, Rutter K, Staufer K, Kneidinger N, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology. 2016 Aug 9;64(2):556–68.
3. Blasi A, Calvo A, Prado V, Reverter E, Reverter JC, Hernández‐Tejero M, et al. Coagulation Failure in Patients With Acute‐on‐Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio. Hepatology. 2018 Dec 9;68(6):2325–37.
4. Bihari C, Patil A, Shasthry SM, Baweja S, Kumar G, Sarin SK. Viscoelastic test-based bleeding risk score reliably predicts coagulopathic bleeding in decompensated cirrhosis and ACLF patients. Hepatol Int. 2020 Jul 17;14(4):597–608.
5. Ow TW, Fatourou E, Rabinowich L, van den Boom B, Nair S, Patel VC, et al. Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver Disease. Thromb Haemost. 2022 Jun 12;122(06):1006–16.

Disclosure

The reagents for the ROTEM analyses were sponsored by Werfen. This study received a Gilead fellowship, and K.F. received a BSTH-CSL Behring encouragement award.

Introduction

Pancreatic exocrine insufficiency (PEI) is a condition characterized by inadequate secretion or activity of pancreatic enzymes, resulting in the maldigestion and malabsorption of nutrients. While PEI is most commonly associated with chronic pancreatitis and cystic fibrosis, it also occurs frequently in the context of pancreatic and peri-pancreatic malignancies. In patients with pancreatic cancer PEI arises due to direct tumor infiltration, ductal obstruction, parenchymal destruction, or as a consequence of surgical resection. Other gastrointestinal malignancies, such as ampullary or biliary tree cancers, may also contribute to PEI through similar mechanisms. Importantly, PEI in cancer patients is often under-recognized, despite its significant impact on nutritional status, quality of life, and overall prognosis. Timely identification and management of PEI in malignancy-associated cases is crucial to optimize clinical outcomes and support ongoing cancer therapies.

Aims & Methods

The objective of this study is to assess the incidence of PEI in patients with biliopancreatic and ampullary tumors, to explore potential differences in PEI occurrence based on tumor location and to investigate possible associations between PEI and relevant biomarkers.
We conducted a retrospective observational analysis of a consecutively recruited patient cohort including patients diagnosed with biliopancreatic and ampullary tumors at a tertiary care hospital between 2016 and 2024.
PEI was defined as fecal elastase-1 (FE-1) levels below 100 µg/g.
At the time of diagnosis, we collected data on demographic characteristics, tumor-related variables, the incidence of PEI, and serum nutritional markers.

Results

We included 408 patients with malignancies potentially associated with PEI. Of these, 54.2% were male, with a mean age of 72 years (range: 38–101) and a mean body mass index (BMI) of 25.45 (SD ± 4.28).
The types of malignancies included were pancreatic ductal adenocarcinoma (PDAC) in 63.5% of patients, cholangiocarcinoma (CCA) in 23.8%, ampullary tumors in 9.8%, and gallbladder tumors in 2.9%. The overall incidence of PEI at the time of diagnosis was 38.2%. Among subgroups, the incidence was 51.4% in PDAC patients, 13.4% in those with CCA, and 25% in those with ampullary tumors. PEI incidence was significantly associated with elevated HbA1c (>5.8%, p<0.01) and Ca 19-9 levels (>37 U/mL, p<0.01).
In PDAC, tumors located in the pancreatic head were associated with a significantly higher incidence of PEI (58.8%) compared to tumors in the body (27.8%) and tail (21.7%) (p<0.01). In this subgroup, PEI was significantly associated with elevated HbA1c (>5.8%, p=0.03), elevated Ca 19-9 (>37 U/mL, p=0.04), and elevated bilirubin (>1.2 mg/dL, p<0.01).
In contrast, among CCA patients, no significant differences in PEI incidence were observed based on tumor location, and no significant associations were found between PEI and the clinical or laboratory variables analyzed .

Conclusion

• PEI is observed not only in patients with PDAC but also in those with CCA and ampullary tumors at the time of diagnosis.
• Given the high incidence of PEI in tumors located in the pancreatic head, empirical pancreatic enzyme replacement therapy should be considered in this subgroup.
• In PDAC patients, the presence of PEI is significantly associated with endocrine dysfunction, hyperbilirubinemia secondary to biliary obstruction and elevated Ca 19-9 levels.