Clinical Case Summary

Biliary pathology is a frequent motive for consultation in hospitals, and abdominal ultrasound is the first line-imaging test for its study. The genetic syndrome LPAC (Low Phospholipid-Associated Cholelithiasis) leads to the development of intrahepatic lithiasis. In this syndrome, there is a decrease in biliary phospholipids secretion caused by a mutation in the ABCB4 gene, responsible for a dysfunction of the MDR3 transporter. Despite being considered a rare entity, it accounts for 1-5% admissions for biliary pathology, affecting young women more frequently.
Two of three clinical criteria must be met for its diagnosis: symptoms onset before the age of 40, recurrence after cholecystectomy and compatible ultrasound appearance (presence of intrahepatic hyperechogenic spots, "comet tail" images or intrahepatic lithiasis with acoustic shadowing). Identification of the ABCB4 gene mutation is not a diagnostic criterion since it only appears in 50% of patients. Medical treatment with ursodeoxycholic acid is effective and cholecystectomy can be avoided.
We present a 23-year-old male who consulted for epigastric pain associated with vomiting. Laboratory tests showed elevation of amylase greater than three times above the upper limit of normal, which allowed the diagnosis of acute pancreatitis. Liver profile, calcium and triglycerides were within normal limits. The patient had no previous alcoholic intake. Abdominal ultrasound ruled out cholelithiasis but identified multiple intrahepatic hyperechogenic spots and "comet tail" signs. The patient was diagnosed with LPAC syndrome and treatment with ursodeoxycholic acid was initiated. During follow-up he did not present new episodes of biliary symptomatology.
The detection of the typical ultrasound signs of LPAC syndrome is the main tool for its suspicion. This disease is not as uncommon as it may seem, so it is essential to think about it in order to make a correct diagnosis and treatment of these patients.

References

Ultrasound image of intrahepatic lithiasis

Clinical Case Summary

Pancreatic cystic lymphangioma is extremely rare, accounting for less than 5% of pancreatic cystic neoplasms and less than 1% of all lymphangiomas.¹
A 51-year-old female presented with complaints of recurrent abdominal pain for 4 weeks. She was previously misdiagnosed as acute pancreatitis complicated with pancreatic pseudocyst. There was no history of trauma. Dynamic MRI on the abdomen revealed a large, encysted collection at the pancreatic body suggesting a query pancreatic pseudocyst. EUS examination revealed a large cystic lesion at the body of the pancreas. The cyst was multilocular with characteristic multiple thin septa within the lesion (Figure 1). EUS-FNA with 22-G needle was done with aspiration of about 20 ml of cyst fluid, divided into two bottles, one for cytology examination and mucin stain while the second bottle for Amylase, CEA and TG levels. Aspiration fluid was serous yellowish in colour, with negative string sign. Also, a large focal lesion within the spleen was also seen.The biochemical evaluation of the aspirated cystic fluid revealed low amylase and CEA, and high TG levels. Cytopathological examination showed fairly cellular material featuring numerous predominantly small lymphocytes. There were no epithelial, atypical, or malignant cells. IHC staining was positive for CD-31 and CD2-40. Alcian blue mucin stain was negative. The diagnosis of pancreatic cystic lymphangioma was made based on EUS, cytological and biochemical examination with IHC features. Since, lymphangiomas are benign tumors without malignant potential, treatment depends on the symptoms. Lymphangioma can encroach on adjacent organs and need surgical resection. To relieve symptoms of abdominal, distal pancreatectomy and splenectomy was discussed, but patient refuse surgery. Multidisciplinary team decided a conservative management with a follow-up by dynamic MRI and EUS within 6 months.

References

1. Chen D, Feng X, Lv Z, Xu X, Ding C, Wu J. Cystic lymphangioma of pancreas: A rare case report and review of the literature. Medicine (Baltimore). 2018 Jul;97(28): e11238. doi: 10.1097/MD.0000000000011238.

Clinical Case Summary

Caudate lobe hypertrophy is a common finding in cirrhotic liver, although giant variants are rare. Nevertheless, any lesion on a cirrhotic liver warrants consideration for hepatocellular carcinoma (HCC).
This case involves a 28-year-old male patient irregularly followed up at our center for secondary biliary cirrhosis. With a history of intrahepatic bile duct paucity due to Alagille syndrome since neonatal age, he is a current smoker (10 pack-years) with no alcohol abuse. After three years lost to follow-up, the patient presented with a gradual 4-month onset of jaundice, dark urine, and upper right quadrant discomfort. Laboratory findings revealed worsening liver function tests: total bilirubin 11.5 mg/dl (vs 2.5 mg/dl), predominantly conjugated 7.6 mg/dl (vs 1.7 mg/dl), alkaline phosphatases 3.3x ULN (vs 2.6x ULN), gamma-glutamyl transferase 6.4x ULN (vs 4.5x ULN), aspartate aminotransferase 3.8x ULN (vs 1.7x ULN), alanine aminotransferase 1.5x ULN (vs 1.3x ULN).
The 4-phase CT scan revealed a dysmorphic liver with a large mass spanning segments 4, 5, 6, 7, and 8, measuring 130x100mm. The mass exhibited arterial enhancement without late phase washout and no evidence of a capsule. This mass displaced the hepatic veins and abutted the inferior vena cava and portal branches, without signs of invasion. MRI showed a similar appearance with no diffusion restriction. Initially suspected as HCC, the mass was classified as LIRADS-4. Alpha-foetoprotein level was normal. CT-guided biopsy retrieved multiple 41mm samples. Histopathological findings indicated annular fibrosis with histological cholestasis and no malignant cells. Therefore, the established diagnosis was caudate lobe hypertrophy, following a multidisciplinary team discussion and review of radiological features.
Despite this entity's rarity, biopsy seems crucial to rule out HCC, especially with abnormal vascular behavior like arterial enhancement, to avoid overtreatment.

Clinical Case Summary

A 74-year-old, female patient was referred to the study center for pancreatic cysts. Magnetic resonance imaging revealed multiple pancreatic cysts up to 15 mm in size distributed from the pancreatic head to the pancreatic tail and enlargement of the main pancreatic duct diameter to 8 mm. T1- and T2-weighted imaging demonstrated showed a 10 mm mass with iso-intensityin the main pancreatic duct in the pancreatic body with diffusion restriction on diffusion-weighted imaging. Endoscopic ultrasonography also demonstrated a mass located in the main pancreatic duct in the pancreatic body, but determining whether the tumor was located in the pancreatic duct or was an extension of the intraparenchymal lesion into the main pancreatic duct was difficult. On contrast-enhanced abdominal computed tomography, the mass was difficult to identify as a lesion because it showed the same contrast as the surrounding pancreatic parenchyma. Endoscopic retrograde choangiopancreatography revealed enlargement of the duodenal papillary entrance, mucus discharge, and a mass-like, translucent image with an irregular surface in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration led to the diagnosis of adenocarcinoma, and a distal pancreatectomy was performed on the assumption that the lesion derived from IPMN. Pathological analysis led to the diagnosis of IOPN consisting of papillary cells with an eosinophilic cytoplasm, positive immunostaining for MUC5AC and MUC6, and partially positive staining for MUC1 and HepPar-1. The mass was determined to be within the pancreatic parenchyma by comparing a resection specimen with preoperative images. Fusion gene analysis revealed the presence of ATP1B1-PRKACA, confirming the diagnosis of IOPN.
It is important always to bear in mind the possibility of IOPN if pancreatic cysts are observed. IOPN is relatively rare, and more cases are needed for a better understanding of this disease.

References

Aatur D. Singhi, Laura D.Wood, Emma Parks, Michael S.Torbenson, Matthaus Felsenstein. Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct : Gastroenterology. 2020 Feb ; 158(3) : 573-582.
Eriko Ikeda. Histological Classification of Intraductal Papillary Mucinous Neoplasms of the Pancreas : Journal of Biliary Tract & Pancreas. 2020 ; 41(1) : 27-31

Introduction

Colorectal polyposis, characterized by more than 10 adenomas, indicates a higher risk of malignancy and necessitates more frequent screening and genetic assessment. However, there are still a large number of polyposis patients with negative genetic test results. This study aimed to explore the risk genetic variants associated with non-hereditary colorectal polyposis through a genome-wide association study (GWAS).

Aims & Methods

Among patients who underwent colonoscopy at a single referral university hospital from January 2012 to September 2021, a total of 638 patients with 10 or more biopsy-proven cumulative polyps on colonoscopies and without genetic mutations or family history related to colorectal polyposis were included in this study. For the control group, a total of 7087 people who underwent colonoscopy for the purpose of health check-up at the Korea Medical Institute and were normal at least twice in a row were included. To find susceptible loci to non-hereditary colorectal polyposis, GWAS was performed and a genome-wide p-value threshold of 5 × 10^-7 was set to assess statistical significance.
We compared the genetic differences between two groups of patients with non-hereditary colorectal polyposis: those with 10 or more polyp recurrences observed during follow-up colonoscopies and those without such recurrences. We utilized SNPs that were identified as risk variants for non-hereditary colorectal polyposis in this GWAS. For each SNP, we defined the risk allele as the allele associated with increased risk of non-hereditary colorectal polyposis as identified in this GWAS. Genotypes were coded as 0, 1, or 2 based on the number of risk alleles identified at each SNP. We used a polytomous logistic regression model to identify SNPs that significantly increased the risk of polyp recurrence compared to the group without recurrence. Results of all regression analyses were adjusted for age, sex, BMI, smoking history, alcohol consumption history, family history of cancer, history of cancer other than colorectal cancer, comorbidities, and history of medication use.

Results

A total of 71 risk variants were discovered, which were new single-nucleotide polymorphisms (SNPs) not found in previous GWAS associated with colorectal cancer and polyp (Figure 1). 5 genes (UPF3A, BICRA, CBWD6, PDE4DIP, ABCC4) nearest or overlapped with 7 SNPs (rs566295755, rs2770288, rs1012003, rs201270202, rs71264659, rs1699813, rs149368557) previously reported directly or indirectly related to the development of colorectal cancer were proven to be risk variants significantly associated with non-hereditary colorectal polyposis. In addition, two new genes (CNTN4, CNTNAP3B) that have not previously been reported to be associated with colorectal cancer or polyp were newly identified.
The SNP rs149368557 was identified as being significantly associated with an increased risk of polyp recurrence in non-polyposis hereditary colorectal cancer (p-value: 0.049, odds ratio: 2.991, 95% confidence interval: 1.006–8.899).

Conclusion

In this study, we found 71 novel risk variants associated with non-hereditary colorectal polyposis. The SNP rs149368557 was identified as being significantly associated with an increased risk of polyp recurrence in non-hereditary colorectal polyposis. The risk variants and genes discovered in this study might be utilized as novel targets to prevent colorectal cancer in the future.

Introduction

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) offers advantages over duodenal stenting and surgical bypass. EUS-GE technique, however, remains non-standardized. A parallel enteric tube (PET) facilitates luminal distention, a critical step during EUS-GE.

Aims & Methods

We primarily aimed at standardizing PET-assisted EUS-GE, secondarily assessing reproducibility and outcomes.
Prospective multicenter study on consecutive adult patients with unresectable malignant gastric outlet obstruction undergoing primary EUS-GE between August 2019-April 2021. Hierarchical task analysis predefined procedural steps into tasks and subtasks. Subtasks were further categorized into essential (performed in all centers and in over 85% of the procedures) or optional. Subtask methodology was considered established if performed similarly in all centers or variable if not. Procedure times, injected fluid volume, luminal diameters obtained, accessories used, and clinical outcomes were recorded.

Results

Seven endoscopists performed EUS-GE in 65 patients (50.8% male, median [IQR] age 77.5 [65.7-86.5] years). EUS-GE was categorized into 4 tasks and 10 subtasks (Table 1). Five essential subtasks involved an established methodology (guidewire and PET placement, endoscope exchange, delivery system insertion and LAMS deployment).
Technical and clinical success rates were 98.5% and 83.3%, respectively. AEs occurred in 10 (15.4%) patients (2 mild, 7 moderate, 1 severe). Success and AE rates were not different between expert and non-experts. Median (IQR) procedure time was 26.2 (19.7-37.1) min. The short and long axis of the targeted small bowel loop was 27 (23-30) x 40 (33-60) mm. Procedure time was longer (35 [30.6-43.7] vs 21.8 [16.4-29.5] min, p<0.001) and injected fluid volume higher (510 [439-870] vs 415 [255-480] ml, p=0.01) in non-experts.

Table 1. Proposed taxonomy for the PET-assisted EUS-GE

Conclusion

PET-assisted EUS-GE was standardized, identifying its key steps and technique variants. PET-assisted EUS-GE appears to be a reproducible procedure among advanced endoscopists with different levels of experience. (Clinical Trials Identification Number: NCT04660695).

Disclosure

Carlos Chavarríareceived research and training support by a grant from The Foundation of the Institute of Health Sciences Studies of Castilla y León (IECSCYL).
Vanessa Martín-Álvarezhas nothing to declare.
José Ramón Aparicio is a consultant for Boston Scientific.
Jose Carlos Subtil has nothing to declare.
Francisco Javier Garcia-Alonso has nothing to declare.
Juan J. Vila is a consultant for Boston Scientific and speaker for Cook Endoscopy and Olympus.
Belén Martínez-Moreno has nothing to declare.
Victoria Busto-Bea has nothing to declare.
Ramon Sanchez-Ocaña has nothing to declare.
Carlos de la Serna-Higuera has nothing to declare.
Manuel Perez-Miranda Miranda is a consultant and speaker for Boston Scientific, Olympus, and M.I.Tech.

Clinical Case Summary

Introduction: Inflammatory bowel diseases gather several phenotypes of autoimmune affectation of the GI tract - sometimes they may frame into a polyautoimmune syndrome (PAS).
Case description: We present a 28-year-old man with nephrotic syndrome, autoimmune hepatitis/primary biliary cholangitis overlap syndrome and alopecia areata universalis, who was on cyclosporine and budesonide.
The patient was admitted with chronic bloody diarrhea and weight loss. He had anemia, hypoalbuminemia and increased CRP; fecal calprotectin (FC) was 4500ug/g. CT scan showed concentric colon thickening. Endoscopic studies showed deep, exudative ulcers in the colon and rectum - biopsies showed chronic active colitis.
Previous immunosuppressive therapies were stopped and prednisolone was begun. Biopsies tested positive for CMV and antivirals were started. The patient improved and was discharged home on steroids.
This was assumed to be a case of unclassified inflammatory colitis with concurrent CMV colitis. In the following months, the patient was re-hospitalized 5 times for severe exacerbations with partial response to steroids and new CMV reactivations. Infliximab was started but discontinued due to loss of response; azathioprine therapy was tried but stopped due to adverse reaction.
It was decided to start tofacitinib. After 6 months of therapy, he is asymptomatic, regaining weight and recovering body hair. FC is 1191ug/g, with no other analytical changes.
Genetic tests show a possible pathogenic variant in LRBA gene (linked to immunodeficiency type 8 with autoimmunity). The LRBA deficit study has been expanded.
Conclusion: This case highlights the complexity of patients with PAS and the need for a multidisciplinary approach. It also proves the efficacy of tofacitinib in this patient, having prevented new admissions so far, with important clinical/analytical improvements. If LRBA deficiency is proven, abatacept may be considered for treatment as it is effective in most of these patients.