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

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

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

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

We present the case of a 68-year-old man who presents with abdominal pain and constitutional syndrome after two months. Faecal occult blood test is positive, so a gastrointestinal endoscopic study is proposed. Complete colonoscopy is normal. In the upper endoscopy, dilated lymphatics with irregular appearance are observed in the second duodenal portion, so biopsies are taken. Histological study of duodenal biopsies shows infiltration by metastatic adenocarcinoma of the lung (positive cytokeratin 7 and TTF1). The study is completed with computed tomography (CT), which objectifies thoracic adenopathies and a mass in the right lower lobe compatible with lung neoplasia.
Metastatic spread of lung cancer may involve any organ, but metastases to the gastrointestinal tract, particularly the duodenum, are considered unusual.¹ Small bowel metastases usually originate from melanoma or carcinoma of the cervix, uteri, ovary, or breast.¹ However, intestinal metastases have been described in 11% of autopsy lung cancer studies, suggesting that this situation is not as rare as it is thought to be.¹ This could be explained because intestinal metastases are often asymptomatic.¹ Less than 0.5% of the metastatic cases are symptomatic.²
When metastasis to the gastrointestinal tract occurs, the findings are nonspecific. The most common symptoms are abdominal pain, cramping, nausea, vomiting, weight loss, and constipation.³ Possible complications of these metastases include perforation, obstruction, and hemorrhage.^1,3 Abdominal imaging studies, as the CT, have a low sensitivity for detecting gastrointestinal metastases, visualized as a wall thickening or masses.³ However, previous cases of gastrointestinal metastases of lung cancer with the appearance of duodenal lymphatic ectasia have not been found in the literature. So, this case should be taken into account to remember that intestinal lymphangiectasia, albeit infrequently, could be the first sign of malignancy.

References

1. Lin HC, Yu CP, Lin HA, Lee HS. A case of lung cancer metastasized to the gastrointestinal anastomosis site where the primary gastric cancer was resected 17 years ago. Lung Cancer 2011;72(2):255-7. doi: 10.1016/j.lungcan.2011.02.005.
2. Tanriverdi O, Alkan A, Ozseker B, Solak-Ozseker H, Kilinc RM. Synchronous duodenum and descending colon metastasis from primary lung neuroendocrine small-cell carcinoma: A case report and review of the literature. J Oncol Pharm Pract 2020;26(6):1524-9. doi: 10.1177/1078155220904133.
3. Ahmed A, Nasir UM, Donna PD, Swantic V, Ahmed S, Lenza C. A rare presentation of poorly differentiated lung carcinoma with duodenal metastasis and literature review. Case Rep Gastroenterol 2020;14(1):186-96. doi: 10.1159/000506927.

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

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus. Major adverse cardiovascular events (MACE) have been associated with diseases of chronic inflammation. Data on MACE from large population-based cohorts of biopsy-proven EoE are lacking.

Aims & Methods

The aim of this study was to investigate the association between EoE and MACE. It included all Swedish adults with EoE (1990-2017) without a record of previous cardiovascular disease (CVD) (n=1,546, with follow-up until 2019). EoE was defined from prospectively recorded esophageal histopathology reports from all Swedish pathology departments (n=28) in the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Individuals with EoE were matched with up to five general population reference individuals (n=7,281) for age, sex, calendar year and county without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACEs (any of ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. In secondary analyses, individuals with EoE were compared to their siblings to account for residual confounding.

Results

The majority of individuals with EoE were male (75%), and the median age at EoE diagnosis was 37 years (IQR 19-51). Over a median of 6.0 (IQR 4.6-8.0) years of follow-up, 65 (4.2%) MACE events were observed in patients with EoE and 225 (3.1%) in reference individuals, corresponding to 6.4 vs. 4.7 events per 1,000 person-years (incidence rate difference: 1.7, 95%CI=0.0-3.4), respectively. No significantly higher overall risk (aHR=1.14, 95%CI=0.86-1.51) of MACE outcomes. No significant differences between age, sex and follow-up time were observed. When adjusting for relevant CVD medication and sibling comparison, results were similar.

Table 1 Incidence Rates, Absolute Rate Differences and Hazard Ratios for incident Major Adverse Cardiovascular Events in patients with Eosinophilic Esophagitis compared to general population reference individuals 1990-2019
		Reference individuals	EoE
		N=7 281	N=1 546
	MACE outcomes*
	Incident events (%)	226	65
	Incidence rate per 1000 py (95%CI)	4.7 (4.1-5.4)	6.4 (4.9-8.1)
	Absolute rate difference per 1000 py (95%CI)	0 (ref.)	1.7 (0-3.4)
	Unadjusted HR# (95%CI)	1 (ref.)	1.37 (1.04-1.80)
	Adjusted HR (95%CI)	1 (ref.)	1.14 (0.86-1.51)

CI, confidence interval; EoE, eosinophilic esophagitis; HR, hazard ratio; MACE, major adverse cardiovascular events; py, person-years

^*Includes ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality.
^#Adjusted for age, sex, calendar year, county of residence at index date, country of birth (Nordic country or other), educational level (compulsory school, upper secondary school or college/university), ≥1 metabolic disease (diabetes, obesity, hypertension or dyslipidemia), chronic kidney disease, atopic dermatitis, celiac disease and chronic respiratory disease (chronic obstructive pulmonary disease or asthma) diagnosis.

Conclusion

Individuals with biopsy-proven EoE had no increased risk of MACE outcomes compared to general population or sibling comparators. The absence of any association with MACEs in our study may be reassuring for patients with EoE.

Disclosure

Dr. Forss has served as a speaker and advisory board member for Janssen corporation. Dr. Uchida is a medical advisor for Sanofi-Regeneron and AstraZeneca. Dr. Roelstraete has no conflicts of interest. Dr. Ebrahimi has served as advisory board member for Boehringer Ingelheim. Dr. Garber do not have any conflicts of interest to declare related to this study. Dr. Sundström reports stock ownership in Anagram kommunikation AB and Symptoms Europe AB outside the submitted work. JFL has coordinated an unrelated study on behalf of the Swedish IBD quality register (SWIBREG). This study received funding from Janssen corporation. JFL has also received financial support from MSD to develop a paper reviewing national healthcare registers in China, and has ongoing discussions with Takeda about a celiac disease project.