Introduction

Biliary diseases are an important source of morbimortality for patients, as well as a burden for the healthcare system. In Spain they represent the main cause of hospitalization (2018: 104551 admissions, 81400 cholecystectomies). The genetic syndrome LPAC (low phospholipid-associated cholelithiasis) is a poorly known and considered as infrequent condition,
that involves the development of hepatolithiasis due to mutations in the ABCB4 gene, which encodes the MDR3 protein that functions as a biliary transporter. Its treatment with bile salts avoids symptoms, admissions and the need for surgery. Our aim is to determine its incidence and characteristics in our center.

Aims & Methods

We conducted an ambispective study between February 2021 and September 2022. To be eligible, the patients had to fulfil at least two of the following: onset of biliary symptoms before the age of 40 years; recurrence of symptoms after cholecystectomy; image of intrahepatic macro- or microlithiasis (hyperechoic foci, comet-tail images, biliary sludge alongside intrahepatic bile ducts). Demographic, clinical, ultrasound and genetic characteristics (analysis of MDR3 gene mutations) were analyzed, as well as their incidence among hospital admissions.

Results

36 patients with LPAC were enrolled (Table 1). 6 of them were identified among 237 patients admitted to the for biliary causes in the last 9 months, which represents an incidence of 2.5% (95% CI: 1.17-5.41). By age subgroup, the incidence was 16.7% among those admitted <40 years and 9.1% among those <50 years. Considering only women, the incidence was 21%
among those admitted <40 years and 15.8% among those <50 years.
The ultrasound characteristics were also analyzed. A trend was found between macrolithiasis with acoustic shadowing and presence of MDR3 mutations (42.9% vs 14.3%), although the differences were not statistically significant.
All patients remained asymptomatic and with no need of hospital readmissions after treatment with ursodeoxycholic acid was initiated.

Conclusion

LPAC syndrome is not as uncommon as it might seem, especially among individuals younger than 40 years old admitted for biliary diseases, and mostly women. Its correct diagnosis based on simple criteria would avoid a large number of hospital admissions and unnecessary cholecystectomies.

References

1. Observatorio de resultados - Portal de Salud de la Comunidad de Madrid. Índice de colecistectomía laparoscópica. Sanidadmadrid.org [Internet, citado a 22 de febrero de 2023].
2. Subdirección General de Información Sanitaria, Ministerio de Sanidad. Registro de Actividad Sanitaria Especializada (RAE-CMBD): Actividad y resultados de la hospitalización en el Sistema Nacional de Salud Año 2018. 2021 feb.
3. Dong C, et al. Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities. JHEP Rep. 2020 Nov 6;3(2):100201.
4. Goubault P, et al. Low-Phospholipid Associated Cholelithiasis (LPAC) syndrome: A synthetic review. J Visc Surg. 2019 Sep;156(4):319-328
5. Su S, Trinh A, Metz AJ, Speer T, Simkin P, Buchanan D, Boussioutas A, Gibson R. Targeted liver ultrasound performed by an expert is the pivotal imaging examination for low phospholipid-associated cholelithiasis. Eur J Gastroenterol Hepatol. 2023 Mar 1;35(3):327-332
6. Biyoukar M, Corpechot C, El Mouhadi S, Chambenois E, Vanderbecq Q, Barbu V, Dong C, Lemoinne S, Tordjman M, Jomaah R, Chazouilleres O, Arrivé L. ABCB4 variant is associated with hepatobiliary MR abnormalities in people with low-phospholipid-associated cholelithiasis syndrome. JHEP Rep. 2022 Sep 21;4(11):100590

Introduction

Caroli disease (CD) is a rare congenital disease defined by the presence of segmental dilations in the intrahepatic bile ducts. It is called Caroli syndrome (CS) when it is associated with liver fibrosis or cirrhosis. It is often diffuse, rarely localized to a single lobe of the liver.
The aim of this study was to describe the epidemiological, clinical and therapeutic aspects as well as the observed complications associated with this pathology

Aims & Methods

We collected patients followed for CD or CS in the gastroenterology department of the Tahar Maamouri University Hospital in Nabeul from January 2008 to December 2018. We retrospectively collected epidemiological, clinical, radiological, therapeutic and evolutionary data.

Results

We collected 8 patients: 4 men and 4 women whose average age was 64 years (38 -79 years). The circumstances of discovery were an acute cholangitis in two patients and biliary colic in six. The average time between the onset of symptoms and definitive diagnosis was 10 months with extremes ranging from 1 month to 10 years. A morphological assessment (abdominal ultrasound, abdominal CT or Biliary MRI) was carried out in all patients. It showed dilation of the intrahepatic bile ducts (IHBD) in all cases. It was diffuse in four cases and localized to the left in 4 cases. It was associated with intrahepatic stones in 50% of patients (N=4). Gallstone lithiasis was associated in 38% of cases (N=3). Polycystic kidney disease was observed in 25% of patients (N=2). All patients had normal renal function. Two patients had signs of portal hypertension consistent with a Caroli syndrome. In our series, complications were observed in 50% of cases such as: iterative attacks of acute cholangitis in two patients, acute pancreatitis due to a biliary lithiasis in one patient and a case of liver abscess in one patient. Episodes of cholangitis were controlled by appropriate antibiotic therapy and ursodeoxycholic acid was prescribed in 3 patients at a dose of 15 mg/kg/day for intrahepatic lithiasis. Surgical treatment was carried out in 4 patients, consisting of a left hepatectomy in 3 patients with localized disease and a choledocotomy with hepaticojejunal anastomosis in one patient for lithiasis of the main bile duct. Endoscopic sphincterotomy was performed in 2 patients: one for residual lithiasis of the common bile duct in and one as sequential treatment. The median follow-up was 84 months, two deaths were observed: one secondary to hepatocellular failure and the other secondary to uncontrolled septic shock. In our series there was no case of cholangiocarcinoma.

Conclusion

The diagnosis of CD is often late. It should be considered in the presence of abscesses or recurrent cholangitis associated with the dilatation of the bile ducts. Hepatectomy of localized forms protects against septic complications and degeneration. Liver transplantation remains to be developed to treat patients with a diffuse form.

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.

Introduction

Endoscopic ultrasound (EUS)-guided sampling is considered the gold standard for the cyto-histological diagnosis of solid pancreatic tumours. Development of new needles over the last years has improved the diagnostic accuracy of EUS-sampling.

Aims & Methods

Aim of our study was to evaluate the accuracy of EUS-sampling for the cyto-histological diagnosis of solid pancreatic tumours in clinical practice.
Methods: Patients who underwent EUS-sampling for the evaluation of solid pancreatic tumour over the last 13 years were identified from a prospectively collected EUS registry and included in the study. EUS was performed with linear Pentax echoendoscopes and Hitachi systems. Tissue acquisition was performed with standard cytology needles (19-gauge, 22-gauge, and 25-gauge) and core needles [ProcoreTM, Franseen and Fork-Tip] (19-gauge, 20-gauge, 22-gauge, and 25-gauge). Samples were collected in a cytological solution (Cytolit®) and processed for cyto-histological evaluation. Results are shown as mean ± standard deviation and percentages. Diagnostic accuracy for malignancy was analysed using the histopathological analysis of the surgical specimens, and the clinical and radiological long-term follow-up in non-operated patients, as gold standard.

Results

1072 patients were included in the study (mean age 67.6 years, range 17-92, 596 male). Size of solid pancreatic lesions was 33.4 ± 15.2 mm. 617 tumours were located in the head of the pancreas, 339 in the body, 83 in the tail and 33 in the uncinate process. Cytology needles were used in 543 patients (50.7%) and core needles in 529 (49.3%). Mean number of needles passes was 1.7 ± 0.8. On-site evaluation of samples was done in 224 (20.9%) cases. 916 (85.4%) masses were finally classified as malignant, whereas 156 (14.5%) were considered benign. Global sensitivity, specificity and overall accuracy for malignancy were 86.5%, 100% and 88.4%, respectively. Obtained sensitivity and overall accuracy were higher with core needles compared with cytology needles (89.4% vs 83.5%, and 90.7% vs 86.2%, respectively).

Conclusion

EUS-guided sampling is an accurate technique for the cyto-histological diagnosis of solid pancreatic tumours. Diagnostic yield reached in clinical practice is superior with core needles than with cytology needles.

Disclosure

Julio Iglesias-Garcia: Advisor Pentax, FujiFilm & Mediglobe

Introduction

Pancreatic cyst prevalence is about 2% to 3% in the general population(1,2). It is important to classify them accurately, given the fact that in premalignant lesions surgery could be curative. On the other hand, unnecessary pancreatic surgery could be associated with significant morbidity. The mucinous cysts are considered the premalignant types, traditionally the carcinoembryonic antigen (CEA) has been described as the analysis of cyst fluid to discern them from the non-mucinous. Recently, the cyst glucose value has been described as a better discriminant, however, there are different cut-off levels founds across the studies(3). The distribution of glucose in the body is almost uniform (4), a higher metabolic rate within a cyst translates into lower intracystic glucose, which correlates with high-grade injury (3). Therefore, we decided to explore the diagnostic performance of the glucometry-to-glucometry cyst ratio.

Aims & Methods

We conducted a prospective cohort from January 2021 to October 2022 at the endoscopy department at the National Institute of Medical Sciences and Nutrition “Salvador Zubiran” (INCMNSZ) in Mexico City. We included patients older than 18 years who underwent endoscopic ultrasound with FNA of a pancreatic cyst and had a fluid analysis of glucose, CEA, and amylase. We performed glucometry on-site on the patient and the cyst fluid with a FreeStyle Optium Neo glucometer. Glucometry to glucometry cyst ratio (glucometry patient/glucometry cyst) was calculated for each patient. Follow-up was performed and a final diagnosis was established by a multidisciplinary team, biopsy or surgical specimen. Finally, we performed a 2x2 table and a ROC curve with Youden index to establish the best cut off for diagnostic performance of glucometry-to-glucometry cyst ratio.

Results

24 patients were included 14 with mucinous cyst diagnosis and 10 with non-mucinous diagnosis, the median age was 58.5 (25-84), and 83% were female. CEA mean was 2331.7± 3359.3 ng/mL for mucinous vs 23.8± 62.6 ng/mL for non-mucinous (p= <0.001). The on-site cyst glucometry was 39.3± 22.1mgdL vs 112± 42.9 for the mucinous and non-mucinous respectively (p= 0.001). The glucometry/cyst glucometry relation was 3.30± 0.84 (mucinous) vs 1.13± 0.69 (non-mucinous), p= 0.001. The AUC was 0.971 (0.915 -1.000), 0.948 (0.853 – 1.00), and 0.964 (0.900 – 1.000) for glucose relation, glucometry, and CEA respectively. The sensitivity, specificity, PPV, NPV, and precision for CEA (192ng/dL) was 70%, 92.8%, 87.5%, 81.2%, and 83.3% while glucometry (<50mg/dL) was 80%, 85.7%, 83.3%, 85.7%, and 83.3%. Notably, the glucometry relation (>2.45) found a 90%, 92.8%, 90%, 92.8%, and 91.6% for the same parameters.

Conclusion

The glucometry-to-glucometry cyst relation is a novel, cheap, accessible, and superior diagnostic approach for the classification of mucinous and non-mucinous pancreatic cysts. Further studies with bigger sample sizes are needed to confirm these findings.

References

1. Laffan TA, Horton KM, Klein AP, et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am J Roentgenol 2008;191:802-7.
2. de Jong K, Nio CY, Hermans JJ, et al. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol 2010;8:806-11
3. Guzman-Calderon E, Md BM, Casellas JA, Aparicio JR. Intracystic Glucose Levels Appear Useful for Diagnosis of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis. Dig Dis Sci 2021
4. Zierler K. Whole body glucose metabolism. Am J Physiol 1999;276:E409-26

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