Clinical Case Summary

A 72-year-old man with a 49-year history of ulcerative colitis (UC), characterized as pancolitis and steroid-dependent, underwent routine surveillance colonoscopy. A congested, ulcerated mass was found in the recto-anal region, with no signs of active colitis in the rest of the colon.
From 2000–2012, he was treated with infliximab, discontinued due to secondary failure, followed by azathioprine (2012–2017), which was stopped due to leukopenia. Since then, he has been on vedolizumab. His medical history also includes hypertension and previous tobacco use.
The patient had been in clinical and biochemical remission for the last two years. Given his long-standing UC and the resection of a lateral spreading tumor (LST) via mucosectomy in 2019 showing hyperplastic mucosa with a focus of low-grade dysplasia, he has been under annual endoscopic surveillance.
At the current exam, a large exophytic, ulcerated mass with superficial necrosis and fibrin (Kudo IV) was seen in the recto-anal region, occupying approximately 1/6 of the luminal circumference and bleeding spontaneously.
Histology revealed a poorly differentiated neuroendocrine carcinoma (NEC) with a high proliferative index (Ki-67: 60%). Staging workup, including CT, pelvic MRI, and endoscopic ultrasound, identified a suspicious regional lymph node, that was confirmed by FDG-PET to be metabolically active.
After multidisciplinary discussion, the decision was made to start systemic chemotherapy without delay. If the patient responds, a total proctocolectomy with permanent ileostomy will be considered.
This case is notable for the rarity of recto-anal NECs, especially in UC patients. Their poor prognosis and unclear association with long-term UC or immunosuppressive treatment complicate management and raise important clinical questions.

References

Images that will be uploaded are: endoscopic findings of the colonic mass, histological specimens of the NEC, radiologic findings (PET)

Introduction

Low Phospholipid-Associated Cholelithiasis (LPAC) syndrome is a rare disorder caused by mutations in the ABCB4 phospholipid transporter, found in biliary canaliculi. These mutations lead to a deficiency in phospholipids and the subsequent precipitation of cholesterol crystals within the small intrahepatic bile ducts. LPAC syndrome can be diagnosed following the emergence of biliary symptoms or through familial screening. The objective of our study is to characterize the epidemiological, clinical, and paraclinical data of patients monitored for LPAC syndrome in our institution and to assess therapeutic responses and outcomes.

Aims & Methods

We collected data from all patients diagnosed with LPAC syndrome at our institution. Diagnosis was established based on the presence of at least two of the following criteria: (1) age at onset of biliary symptoms ≤40 years; (2) presence of hyperechoic intrahepatic foci ("comet tails" or micro-spots); (3) recurrence of biliary symptoms post-cholecystectomy.

Results

10 patients were included. The Average age at diagnosis was 33,6 years, with symptoms typically beginning around age 30. The sex ratio was 2/8 (M/F).a family history of biliary lithiasis and cholecystectomy before the age of 40 were found in 70% of cases . None of the female patients had a history of pregnancy-related cholestasis. 70% of the patients had undergone cholecystectomy prior to their LPAC diagnosis, with recurrence of biliary symptoms before age 40 in all these patients. Clinical presentations upon admission included symptomatic gallstone disease in 5 cases, acute cholangitis due to main bile duct stones in 4 cases, and acute lithiasic pancreatitis in 1 case. Hepatobiliary ultrasound was performed in all patients, revealing comet tail signs in 50% of cases, hyperechoic intrahepatic spots in 20% of cases, and intrahepatic stones in 50% of cases. Biochemical tests showed hyperbilirubinemia in 30% of cases, elevated Gamma-GT and alkaline phosphatase in 80% of cases, and hepatocellular damage in 40% of cases. A mutation in the ABCB4 gene was found in 2-patients.8 patients benefit from An Ursodeoxycholic Acid (UDCA) dosage averaging 11mg/kg, experiencing significant clinical and biological improvements.

Conclusion

LPAC syndrome is a rare pathology in our series, predominantly affecting young, non-overweight women with personal and family history of early biliary stones occurrence . Treatment with Ursodeoxycholic Acid (UDCA) controlled symptoms in the majority of cases.

Introduction

MASLD patients is increasing worldwide and the clinical outcomes of different phenotypes had shown varied especially the occurrence of of liver related events (LRE) or major cardiovascular events (MACE)(Eslam M, et al. Hepato Inter 2020, 14:889–919) In addition, the prognostic factors for LRE. or MACE. are not well studied.

Aims & Methods

Aims: We aimed to study the rate of LRE. or MACE and the predictors for LRE. Or MACE. in MASLD patients with liver biopsy proven.
Methods: In a single-tertiary-center prospective cohort, we collected data of MASLD patients with biopsy-proven who were followed up of at least 1 years at King Chulalongkorn Memorial Hospital during 2005-2022. The primary outcome was the presence of LRE. or MACE. which included cirrhotic complications: acute decompensations; EV/GV bleeding, ascites, hepatic encephalopathy or HCC or acute complications requiring liver transplantation or death. MACE was defined by the occurrence of stroke or acute coronary disease or myocardial infarction. Related baseline characteristics, LSM, FIB-4, and liver biopsy were collected.

Results

Among 286 MASLD patients, the MASLD patients with mean age of 50.1 +/- 14.5 years old (range 19-80 yr.) Male and female were 44% and 56 % respectively. MASLD patients were categorized into 3 groups which were type 2 diabetes mellitus (T2DM) in 119 (41.6%), overweight or obese group in 149 (52.1%), and lean MASLD (BMI<23) in 18 (6.3%). Their baseline characteristics were shown in Table 1.
The average BMI was 41.3 kg/m² (range 19.1-88.7). Other metabolic abnormalities were hypertension in 165 (57.7%), and dyslipidemia in 157 (54.9%). There were 6 cirrhotic cases (2.1%) at diagnosis. Presence of advanced liver fibrosis (TE>12KPA) was found in 15 cases (5.2%). After a mean follow-up of 9.5 years (range 1-19); there were 11 cases (3.8%) developed coronary artery disease and 3 cases (1%) developed stroke. LRE. were present in 7 cases (2.4%) which included acute decompensation (3 cases; 1%), HCC (3 cases; 1%), and death (1 cases; 0.3%). The overall complications of LRE. or MACE. were present in 16 cases (5.6%). By using multivariate analysis, the predictors of LRE. or MACE. were in presence of hypertriglyceridemia (aOR 1.01 (1.00-1.01); p =0.002) and older age (aOR 1.06 (1.01-1.11); p =0.023).

Conclusion

The overall complication of LRE. or MACE. was not uncommon (5.6% of this cohort with a mean follow-up of 9.5 years). Older age and hypertriglyceridemia were predictors of LRE. or MACE. occurrence.

References

Eslam M, et al. Hepato Inter 2020, 14:889–919.

Introduction

Autoimmune pancreatitis (AIP) is a rare disease that can be diagnosed, according to the International Consensus Diagnostic Criteria (ICDC). Contrast-enhanced MRI with MRCP has now largely replaced other imaging techniques and ERCP for the assessment of ductal morphology in AIP. A number of MRI-criteria have been proposed, but due to the rarity of the disease the diagnostic imaging criteria have not yet been systematically validated. Aim of the study is to review and optimize the MR-morphologic diagnostic criteria for AIP in terms of specificity and sensitivity in the diagnosis and differential diagnosis of the pancreaticobiliary system.

Aims & Methods

We analyzed retrospectively hundred-fiftysix (n=156) high-quality MRIs: AIP n=56, chronic pancreatitis (CP) n=25, pancreatic cancer (PDAC) n=25, primary sclerosing cholangitis (PSC) n=25, Non-HPB subjects n=25. The MRI reading was conducted in a blinded fashion, using defined criteria by at least two radiological experts. The statistical analysis was performed by means of Proportion test, Chi-square test or Fisher’s exact test, One-way ANOVA and Cohen’s Kappa Statistic of the level of agreement.

Results

The level of agreement between two readers was moderate to substantial agreement (κ 0.23-0.85). Sausage-like enlargment (Reader 1: Sens 30.91%, Spec 98.98%, NPV 71.85%, accuracy 74.51%; Reader 2: Sens 26.79%, Spec 98.00%, NPV 70.50%, accuracy 72.43%), restricted diffusion (Reader 1: Sens 47.83%, Spec 89.29%, NPV 75.76%, accuracy 74.51%; Reader 2: Sens 56.86%, Spec 73.26%, NPV 74.12%, accuracy 72.30%), delayed enhancement in the venous phase (Reader 1: Sens 8.70%, Spec 83.15%, NPV 63.79%, accuracy 74.10%; Reader 2: Sens 32.61%, Spec 79.31%, NPV 69.00%, accuracy 75.19%), the icicle sign (Reader 1: Sens 10.91%, Spec 100%, NPV 66.67%, accuracy 65.30%; Reader 2: Sens 37.50%, Spec 91.00%, NPV 72.22%, accuracy 71.79%) and hyperenhancement of ductal wall (Reader 1: Sens 14.29%, Spec 96.67%, NPV 67.44%, accuracy 71.90%; Reader 2: Sens 8.51%, Spec 95.45%, NPV 66.14%, accuracy 74.10%) show a good accuracy distinguishing AIP from controls. Apparent diffusion coefficient (ADC) was significantly different between AIP, PDAC and CP (ANOVA). The area under the receiver operating characteristic curve (AUROC) was 0.85 (CI 0.73 – 0.97) and 0.68 (CI 0.51 – 0.85) respectively for CP and PDAC.

Conclusion

Our study showed that the Sausage-like enlargment, restricted diffusion, delayed enhancement in the venous phase, the icicle sign and hyperenhancement of ductal wall show a good accuracy distinguishing AIP from controls.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone in the diagnosis and treatment of pancreatobiliary diseases. However, it carries the risk of complications including potentially fatal post-ERCP pancreatitis (PEP). Despite ongoing efforts, effective strategies for managing PEP remain unestablished. Current guidelines define PEP based on symptoms and findings occurring within 24 hours after ERCP; however, early diagnosis and intervention may prevent its incidence and severity. Recently, urinary trypsinogen-2 (UT2) has emerged as a potential biomarker for early acute pancreatitis, but its role and the optimal timing for PEP remain unclear. Therefore, we aimed to evaluate the diagnostic performance of UT2 at multiple time points following ERCP.

Aims & Methods

This is a single-center prospective observational study conducted at The University of Tokyo Hospital. Patients who underwent their initial ERCP at our institution between February 2022 and June 2024 were enrolled. Patients with choledochojejunostomy, biliary pancreatitis, or those undergoing hemodialysis were excluded. UT2 levels were measured using a rapid dipstick test before ERCP, immediately after, and at 1 and 3 hours post-procedure. Serum amylase (AMY) levels were measured 3 hours after ERCP. We evaluated the diagnostic performance (sensitivity, specificity, and accuracy) of UT2 at multiple time points, for the diagnosis of PEP. PEP was defined as an elevation in pancreatic enzyme >3x upper limit of normal with abdominal pain at 24 hours post-pocedure.

Results

A total of 521 patients underwent initial ERCP during the study period, and 337 were included in the final analysis. The median age was 74 years, and 64% were male. A naïve papilla was present in 89% of patients. The indications for ERCP included bile duct stones (39%), malignant biliary obstruction due to pancreatic cancer (13%) or non-pancreatic cancer (18%), benign biliary stricture (5%), diagnostic pancreatogram (24%), and others (1.2%). EST, EPBD, and EPLBD were performed in 37%, 6.5%, and 4.5%, respectively. Prophylactic pancreatic stent placement and rectal NSAIDs administration were performed in 29% and 20%, respectively. PEP occurred in 10% (mild 8.6%, moderate 1.2%, and severe 0.3%) of patients. UT2 demonstrated a trend toward higher sensitivity compared to AMY (AMY: 52.9% vs. UT2 at 0 h: 52.9%, 1 h: 64.7%, 3 h: 64.7%), while AMY exhibited significantly higher specificity (AMY: 92.7% vs. UT2 at 0 h: 65.3%, 1 h: 64.7%, 3 h: 65.0%) and accuracy (AMY: 88.7% vs. UT2 at 0 h: 64.1%, 1 h: 64.7%, 3 h: 65.0%). Notably, 28.5% of patients were positive for UT2 prior to undergoing ERCP. These patients were significantly older (79 vs. 71 years, P < 0.01), more likely to have pancreatic cancer (19.8% vs. 9.5%, P = 0.02), and less likely to have chronic pancreatitis (3.1% vs. 12.9%, P = 0.01). After excluding 96 cases (28.5%) who were UT2-positive before ERCP, we further evaluated the diagnostic performance of UT2 and AMY. UT2 at 0 h had lower sensitivity compared to AMY (AMY: 54.2% vs. UT2 at 0 h: 37.5%, 1 h: 54.2%, 3 h: 54.2%). In contrast, specificity was similarly high across all markers (AMY: 91.7% vs. UT2 at 0 h: 88.9%, 1 h: 87.1%, 3 h: 87.1%). Diagnostic accuracy was comparable between AMY and UT2 (AMY: 88.0% vs. UT2 at 0 h: 83.8%, 1 h: 83.8%, 3 h: 83.8%).

Conclusion

UT2 showed slightly lower predictive performance for PEP compared to AMY. However, excluding UT2-positive pre-ERCP improved the diagnostic accuracy. The diagnostic performance plateaued at 1 hour after ERCP, suggesting its potential utility in predicting PEP earlier.

Disclosure

The author is affiliated with Nipro Corporation through a labor-related arrangement, but has received no financial support or remuneration related to this study.

Introduction

Chronic pancreatitis is a progressive inflammatory disease characterized by irreversible damage to the pancreas. The etiology of the disease is heterogenous and includes alcohol abuse, smoking, genetic risk factors and autoimmune diseases. Several clinical classification and severity scoring systems have been proposed, but none have been globally accepted or reached broad clinical use. Identifying patients at a higher risk of death is crucial for improving patient care and management.

Aims & Methods

This study aimed to develop a prediction model based on promoter hypermethylation of specific genes and clinical factors to differentiate patients with chronic pancreatitis who are at a higher risk of mortality. Clinical variables such as age, sex, smoking status, alcohol consumption, exocrine insufficiency, and endocrine insufficiency, as well as the methylation status of 16 genes, were analyzed using a backward stepwise Cox regression model. The methylation status was determined by a specialized bisulfite based PCR technique. The final model's performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), and used to determine a risk score for each patients. The “cutpt” package in Stata was used to determine an optimal cut-off, in order to stratify patients into low and high-risk groups. Kaplan-Meier survival curves, and cox regression, and AUC were used to determine the accuracy of the risk groups.

Results

Ninety-seven patients with chronic pancreatitis were included in the study. The final prediction model included age, sex, exocrine insufficiency, endocrine insufficiency, and the methylation status of 5 genes: SFRP2, HIC1, MLH1, RASSF1A, and CDKN2B. The AUC of the model was 0.84, indicating high reliability. The model was superior to a model including only clinical variables (AUC = 0.76), indicating added value of the methylation markers. The optimal cut-off value for the risk score was 7.76. According to this, 67 patients were in the low-risk group, and 30 in the high-risk group. The 5-year survival in the high-risk group was 53% compared to 94% in the low-risk group. Being in the high-risk group was significantly associated with an increased HR of death of 10.2 (95% CI; 4.9-21.1), demonstrating the model's strong prognostic value.

Conclusion

The developed prediction model, which combines clinical factors and gene promoter hypermethylation status, could be a valuable tool for identifying patients with chronic pancreatitis who are at a higher risk of death. This study serves as proof-of-concept of the unexplored potential of methylation analysis in cell-free DNA in chronic pancreatitis. This model can potentially enhance patient care by enabling targeted interventions and monitoring for high-risk individuals, ultimately improving their prognosis and quality of life.

Disclosure

S.D.H., P.H.M., O.T.-U., and H.B.K. declare that they have a patent on a diagnostic panel including the promoter hypermethylation status of 8 genes. Application No. 16161073.8 – 1403 Pancreatic Cancer methylation Markers (18.03.2016)