Introduction

Matched therapy based on comprehensive genomic profiling (CGP) is essential for improving the prognosis of patients with inoperable cancers. Although endoscopic ultrasound-guided tissue acquisition (EUS-TA) has a high sensitivity for the diagnosis of abdominal malignancies, such as pancreatic cancer, it yields a smaller quantity of tissue than that provided by surgical specimens. Consequently, CGP using tissue samples obtained via EUS-TA occasionally fails. In EUS-TA, the optimal method of obtaining and preparing tissue samples appropriate for CGP has not been elucidated.

Aims & Methods

The aim of this study was to determine the optimal EUS-TA method for obtaining samples for a commercially available CGP test. This retrospective study included 107 consecutive cancer patients in whom CGP using FoundationOne CDx (F1CDx) (Foundation Medicine Inc.) was attempted using tissue samples obtained via EUS-TA of solid abdominal tumors between June 2019 and January 2023. Franseen, Fork-tip, or forward-facing bevel needles were used for EUS-TA. Regarding the methods used during EUS-TA, we focused on needle size, aspiration technique, macroscopic on-site evaluation (MOSE) result, and slide preparation method. Macroscopic visible core (MVC) length was measured using MOSE in all patients. In the first half of the study period, each specimen obtained from each pass during EUS-TA was embedded in a separate formalin-fixed paraffin-embedded (FFPE) block (separate embedding), and slides created from the FFPE block that contained the largest amount of tumor tissue were sent for F1CDx testing. In the second half of the study period, all specimens from all passes were embedded in a single FFPE block (combined embedding). Foundation Medicine Inc. reported the results of the analysis, which were categorized as “passed,” “qualified,” or “failed.” “Qualified” indicated a partial deficiency in the analytical results, such as microsatellite instability. “Passed” and “qualified” were defined as successful F1CDx results, with “passed” indicating a completely successful F1CDx test. We evaluated the relationship between the methods used during EUS-TA and the complete success of F1CDx and investigated factors that predicted a completely successful F1CDx test.

Results

Pancreatic, biliary, and other primary cancers were diagnosed in 87, 17, and 4 patients, respectively. The needle size was 22, 20, and 19 G in 77, 2, and 28 patients, respectively. The stylet slow-pull and suction techniques were performed in 50 and 57 patients, respectively. The median total MVC length in the FFPE block submitted for CGP was 42 mm. Separate and combined embedding was performed in specimens from 35 and 72 patients, respectively. The median total MVC length was significantly longer with combined embedding than with separate embedding (55 vs. 22 mm, p < 0.001). The rate of successful and completely successful F1CDx was 88% and 68%, respectively. Univariable analysis showed that completely successful F1CDx was significantly more frequently achieved with the stylet slow-pull technique (p =0.022), MVC length > 50 mm (p < 0.001), and combined embedding (p = 0.0037). Additionally, multivariable logistic regression analysis revealed that only MVC length > 50 mm independently affected the complete success of F1CDx (odds ratio, 7.7; 95% confidence interval, 2.2-27; p = 0.0013).

Conclusion

In tissue specimens obtained using EUS-TA, MVC > 50 mm can be an indicator of an appropriate sample for F1CDx. To acquire a longer MVC in one FFPE block, combined embedding is recommended.

Introduction

Endoscopic ultrasound (EUS) tissue acquisition requires rapid on-site evaluation (ROSE) to improve diagnostic yield with less needle passes; however, ROSE requires the presence of a cytopathologist and additional cost and time for slide staining and interpretation. Macroscopic on-site evaluation (MOSE) is the direct assessment of the tissue sample provided by EUS-guided fine needle biopsy (EUS-FNB) macroscopically, to detect whether it is sufficient or not.

Aims & Methods

Aim of this study was to evaluate the efficacy of MOSE in terms of tissue acquisition and diagnostic accuracy for abdominal solid lesions
This is a prospective and comparative study including 148 consecutive patients performing EUS-FNB for pancreatic and extrapancreatic solid lesions, randomized by alternate allocation to macroscopic on-site evaluation (MOSE) (74 patients) or to a conventional technique (74 patients), with two passes each. MOSE samples were differentiated into score 0: no visible material, score 1: only necrotic or haematic material, score 2: white core tissue ≤ 2 mm, or score 3: white core tissue > 2 mm. The conventional technique consisted in pushing all the needle content into a test tube for evaluation by the pathologist. In both groups, a 22 Gauge Franseen-tip needle biopsy was used.

Results

The overall diagnostic adequacy was 92.5% (137/148) and accuracy was 86.4% (128/148). The diagnostic accuracy was similar in the two groups: MOSE 87.8% (65/74 lesions), vs. conventional 81.0%, 60/74 lesions, p = 0.34). Regarding diagnostic adequacy, the MOSE technique was 95.9% (71/74 passes) compared to 91.8% (136/148 passes) with the conventional technique, p = 0.04. The accuracy increased according to the MOSE score evaluation: it was 49.3%, 68.9% and 81.3% in patients with score 1, score 2, and score 3, respectively. There was no statistically significant difference between the two groups with conclusive and inconclusive cytopathological results regarding size of the needle, number of needle passes, type of the needle and the specimen acquisition method.

Conclusion

The MOSE score showed a comparable diagnostic accuracy to the conventional technique. However, MOSE allows endoscopists to perform an inspective evaluation of the material, tends to perform better than the conventional technique in terms of diagnostic adequacy, and may potentially reduce the number of passes.

Introduction

Endoscopic ultrasound guided Shear wave elastography (EUS-SWE) is a noninvasive technique to evaluate
organ fibrosis as hardness. Velocity of SWE (Vs, m/s) enables to quantify, and the measured value is
also evaluated with confidence index: VsN (Percentage of the net amount of effective of Vs, %). EUS-SWE has been reported as a useful diagnostic modality for chronic pancreatitis (S Shintani et al JMU 2023). As for pancreatic cancer, previous reports using transabdominal ultrasound have reported only that Vs of pancreatic cancer is elevated, but there are no reports of VsN or using EUS devices. In this study, we examined the characteristics of pancreatic cancer using EUS-SWE.

Aims & Methods

The subjects were patients who underwent EUS-SWE at Shiga University Hospital from April 2019 to December 2022. The retrospective study was conducted with 121 patients (pancreatic cancer, chronic pancreatitis, normal pancreas). EUS-SWE was performed at least 5 times, and the median value was measured. Vs and VsN were measured at central site of tumor cases, and pancreatic body with chronic pancreatitis and normal cases. Histogram analysis (Complexity) at the SWE measurement site was also performed to evaluate tissue heterogeneity. ALOKA ARIETTA 850 (FIJIFILM, Tokyo, Japan) and GF-UCT260 (Olympus Co., Tokyo, Japan) was used.

Results

The subjects were 69 cases of pancreatic cancer (39 males, age: 68.9±10.6 years), 10 cases of chronic pancreatitis (6 males, age: 74.3±5.5 years), and 42 normal cases (22 males, age: 57.5±11.1 years) The EUS-SWE results (pancreatic cancer / chronic pancreatitis / normal) were Success rate (%): 87.2 / 93.5 / 98.1, Vs (m/s): 2.27±0.61 / 2.6±0.67 / 1.68±0.49, VsN (%): 22.6±15.9 / 76.2±21.2 / 79.6±20.6. Complexity: 30.1±12.3 / 23.9±4.8 / 13.5±10.6 indicate that heterogeneity within the tissue is higher in the order of pancreatic cancer > chronic pancreatitis > normal group. VsN and Complexity were inversely correlated, and the higher the tissue heterogeneity, the lower the VsN (r=-0.45, p<0.001, Spearman correlation test).

Conclusion

Vs was increased in pancreatic cancer compared to normal pancreas. However, VsN was more likely to be decreased in pancreatic cancer, which associated with higher tissue heterogeneity. EUS-SWE for pancreatic cancer should consider tissue heterogeneity.

References

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Introduction

Chronic pancreatitis represents a risk for pancreatic cancer with an estimated effect of 16 in the first 2 years, 7.9 in the first 5 years and over 3 in 9 years. The sensitivity of endoscopic ultrasound fine needle aspiration (EUS-FNA) in diagnosing pancreatic malignancy in cases with and without chronic pancreatitis drops from 91.5% to 65.3%. Although contrast-enhanced fine needle aspiration (CH-EUS-FNA) was not statistically superior to standard EUS-FNA in diagnosing solid pancreatic lesions, some emphasis was placed on the usefulness of CH-EUS-FNA in cases of pancreatic masses on chronic pancreatitis.

Aims & Methods

Aim. To assess and compare the diagnostic rate of CH-EUS tissue acquisition (CH-EUS-TA) compared to standard EUS-TA in cases of solid pancreatic masses with features of chronic pancreatitis.

Material and methods. This is a retrospective unicenter study from 2020 to 2022 that included solid pancreatic masses (solid component > 80%) that required EUS-guided sampling and features of chronic pancreatitis that needed EUS tissue acquisition. We excluded patients with previous surgery or chemotherapy for pancreatic diseases, contraindications for tissue sampling or without 1-year follow-up in negative cases. We divided patients in two groups: group 1 with CH-EUS-FNA and group 2 with standard FNA, both using 22G needles. The final diagnosis was based on FNA or surgery results or on 1-year follow-up.

Results

There were 13 patients included in group 1 and 27 patients included in group 2. The sensitivity for malignancy was 85% in group 1 and 80% in group 2. No difference was proved regarding size or mass location, percentage of definitive chronic pancreatitis between groups. The most common lesion location was the head of the pancreas (60%), while the mean mass size was 2,4 cm. Less than 50% of patients (42%) were classified as “Definitive Chronic Pancreatitis” according to Rosemont Criteria. Regarding the severity of disease according to Cambridge Severity Score, the largest group (45% of patients) was the “Cambridge 3” group. 45% of the patients required main bile duct stenting for main bile duct stenosis. A small percent of patients (15%) showed signs of portal hypertension. In group 1, the hypo-enhancement was observed in 38.4% of patients.

Conclusion

In this retrospective series, the CH-EUS-FNA proved to perform similarly with EUS-FNA when chronic pancreatitis features were noticed. Further studies using EUS fine needle biopsy (EUS-FNB) contrast guided procedures are needed in this category of patients.

References

1. Kirkegard J et al. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. Am J Gastroenterol 2017
2. Abdallah MA, et al. Endoscopic Ultrasound Guided Fine-Needle Aspiration for Solid Lesions in Chronic Pancreatitis: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2022

Disclosure

The authors have no conflicts of interest to declare.

Introduction

Contrast enhanced endoscopic ultrasound (CE-EUS) has emerged as an invaluable real time tool in the characterisation and diagnosis of gastrointestinal(GI) lesions but application in therapeutic EUS (post tissue acquisition) remains under evaluated. Bleeding post EUS tissue acquisition(TA) is usually mild, self limiting though serious complications can still occur. We aim to review if application of real time CE-EUS to assess and quantify severity of bleeding has any impact on the clinical outcome and need for intervention.

Aims & Methods

This was a retrospective study of 1597 consecutive patients who underwent tissue acquisition at a single tertiary centre between March 2018 to March 2023. Patients with new onset fluid collection/haemorrhage post tissue acquisition who underwent CE- EUS using Sonazoid contrast agent were included. Information on baseline demographics, pre/post laboratory tests, EUS procedural findings and clinical outcomes were collected. Video recordings of the CE-EUS were reviewed and graded according to the extent of perfusion with presence/absence of contrast extravasation and pseudo-aneurysm.
Severity EUS findings of the fluid/hematoma post CH-EUS injection(observed for at least 90s)
Grade 0 No perfusion noted
Grade 1 Perfusion noted < 50% of total area
Grade2 Perfusion noted > 50% of total area
Grade 3 100% perfusion of the area of concern

Results

60/1597 (4.4%) patients had hematoma/new onset fluid collection post EUS-TA with CE-EUS performed. Overall intervention rate post EUS-TA was 5/1597 (0.31%). 29 patients were subsequently analysed based on video availability and divided into no leak(grade 0) and active leak group(grade1-3). There were no significant differences in the median age (53 vs 64, p = 0.13), Charlson Co-morbidity index (3.5 vs 3, p = 0.561) and antiplatelet usage. There were also no significant differences between lesion size (24.6 vs 31.6, p= 0.246), needle sizes and the number of passes(3 vs 2, p= 0.34). 53% (8/17) of the active leak group had final diagnosis of neuroendocrine/cystic lesions as compared to the non active leak 3/12(25%). Fisher’s exact test used did not show any statistically significant association between haemoglobin drop, need for intervention and death (p=0.413) respectively with the CE-EUS results.

Conclusion

Post EUS Tissue acquisition bleeding is mostly mild and self-limiting. More studies are required to see if CE-EUS can play a objective role in predicting adverse outcomes.

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

Early chronic pancreatitis is a preliminary stage of chronic pancreatitis in “Mechanistic Definition”. However, the diagnostic criteria consist of subjective factors. Endoscopic ultrasound guided shear-wave elastography (EUS-SWE) is a novel imaging modality for the quantification of tissue stiffness. In this study, objective clinical features of ECP patients were examined using EUS-SWE.

Aims & Methods

We selected 34 patients in the ECP group and 53 patients in the normal group who underwent EUS-SWE from April 2020 to December 2021. ECP was diagnosed by JPN criteria in 2019. We used propensity score matching with age and sex, and 22 patients in each group were included in the evaluation. Elastic velocity measured by EUS-SWE (Vs, m/s) in the pancreatic body at least 5 measurements were examined. Each Vs value had a reliability measurement (VsN, %) and >50% was considered reliable. ALOKA ARIETTA 850 (FUJIFILM, Tokyo, Japan) and GF-UCT260 (Olympus, Tokyo, Japan) were used.

Results

The patients were 14 (63.6%) males with a mean age of 66.6 years in both groups. Type 2 diabetes mellitus was observed 18.1% in the ECP group and 22.7% in the normal group, history of alcohol consumption (>60g/day) was 36.4% and 9.1%, respectively. Clinical signs included 90.9% of abdominal pain, 18.2% of a history of acute pancreatitis, and 22.7% of pancreatic exocrine insufficiency in the ECP group. In addition, EUS findings showed 100% of Hyperechoic foci and strands, 54.5% of Lobularity, 68.2% of Hyperechoic duct wall, and 50% of Dilated side branch. The overall kappa values (95% CI) of interobserver reliability (IOR) for each EUS findings was as follows; hyperechoic foci and strands: 0.95 (0.86–1.0), lobularity: 0.67 (0.40–0.94), hyperechoic main duct margin: 0.68 (0.43–0.92), dilated branch ducts: 0.56 (0.27–0.86). Vs values were 2.21±0.56m/s in the ECP group and 1.69±0.36m/s in the normal group, which were significantly higher in the ECP group (p<0.001). The area under the curve for ECP diagnosis was 0.82 (cut off: 2.10, 95%CI: 0.69-0.94). However, Vs values were not useful as a predictor of type 2 diabetes or pancreatic exocrine insufficiency (p>0.05). There was a positive correlation between Vs values and the number of EUS criteria (rs=0.63, p<0.001). In multivariate analysis, history of acute pancreatitis and EUS score (≥2 criteria) were independent factors to increase Vs value.

Conclusion

The tissue velocity evaluated by EUS-SWE showed high elasticity in ECP compared to the normal pancreas. Furthermore, the Vs value was strongly correlated with EUS findings.

References

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