Introduction

Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) can demonstrate microvascularization of the tumors. However, most images acquired from CEH-EUS are interpreted subjectively without quantification by time-intensity curves (TICs) analysis.

Aims & Methods

In this study, we used handcrafted software to quantify CEH-EUS images for objective interpretation of tumor microvascularization to make differential diagnosis of pancreatic tumors feasible.
We analyzed the videos of CEH-EUS for pancreatic tumors from the patients in National Taiwan University Hospital and Far Eastern Memorial Hospital. The convex-type echoendoscope (GF-UCT260; Olympus, Tokyo, Japan) equipped with ultrasound (US) systems (EU-ME2) was used for the procedures. The second generation of US contrast agent with Sonazoid (GE Healthcare, Milwaukee,Wisc), which contains perfluorobutane microbubbles with a median diameter of 2–3 μm, was administered bolus and intravenously with a dosage of 0.015 ml encapsulated gas per kilogram body weight. The videos were recorded in AVI formats with 30 frames/second.
The algorithm for getting TICs includes the following steps:
(1) Circling the region of interest(ROI) in the B-mode
(2) Performing speckle tracking of the ROI in the B-mode
(3) Simultaneously obtaining the intensity of ROI (the mean pixel values in the ROI) in the corresponding contrast-enhanced harmonic image
(4) Outputting TICs after subtracting the baseline intensity (defined as mean TIC in the first 10 s for eliminating the different baseline intensities caused by other settings).
(5) Outputting histogram of pixel values and excel file containing all pixel values from the frame with the highest mean pixel value automatically.
(6) Calculating the standard variance of (5) to represent the heterogeneity inside the ROI.
The speckling tracking composes of searching and matching processes. We used full search for the searching process and normalization cross-correlation for the matching process. By using the hardware of CPU with Intel i7-8750H and GPU with Nvidia GTX 1050 Ti, the computation time was 0.7 ms/frame.

Results

The detailed results were shown in Table 1. We collected 10 and 7 videos of CEH-EUS for pancreatic tumors from NTUH and FEMH respectively in this study. Among them, 9 were diagnosed of pancreatic ductal adenocarcinoma (PDAC), 6 were pancreatic neuroendocrine tumors (PNET), and 2 were autoimmune pancreatitis (AIP). The TICs were obtained through our proposed model. Briefly, there were no significant differences in times to peak, the mean peak intensity, the in-slope tangent and standard deviation of pixel value in ROI (from the frame with the highest mean pixel value) among PDAC, PNET, and AIP. However, there was significant difference in the mean peak intensities of PDAC and non-PDAC (37.88 vs 63.12, p=.031).

Table 1.The results from three kinds of pancreatic tumors based on the proposed model

Conclusion

In this study, there were no significant differences in times to peak, the mean peak intensity, and SD of pixel value in ROI (from the frame with the highest mean pixel value) among PDAC, PNET, and AIP, however there was significant difference in the mean peak intensity between PDAC and non-PDAC group. A study with larger test number is needed in the future for further application.

Disclosure

We have no conflicts of interest to disclose.

Introduction

Current endoscopic ultrasound technologies (EUS) are suboptimal in the assessment of pancreatic cystic lesions (PCLs). We developed a new through-the-needle brush, the "loop brush", to improve the cellular yield, and thereby sensitivity, of EUS fine needle aspiration (EUS-FNA) of pancreatic cysts.

Aims & Methods

We aim to evaluate the "loop brush" safety, robustness, and efficacy.
We performed an in-vivo randomized controlled trial in pigs using artificial cysts. In one group, the loop brush was deployed through a 22G EUS-FNA needle into the cysts. In the control group, cystic punction was performed with standard EUS-FNA. Loop brushes were visually inspected post-procedure. Cytological assessment, cell counting, and hemoglobin analysis were performed in samples from both groups.

Results

Artificial cysts (n=114) were punctured in six pigs, 57 in each group. Neither adverse events nor significant device malfunction occurred during loop brushing. Samples collected with the brush had non-detectable concentrations of hemoglobin in 72% (41/57) of cases, and 26% (16/57) had less than 0.6 g/dL, with no significant difference to the controls (p=0.32). Brushing cell counts were associated with significantly increased cell counts (11.7× median difference, p<.0001). Cytological smears
were diagnostic in 77% of cases in the brushing group, while 54% in the control group (p=0.01, Fisher’s exact test; p=0.006, Chi-square test).

Conclusion

The new loop brush procedure appears to be safe, causing neither significant bleeding nor device malfunction. Samples obtained with the loop brush were suitable for cytological analysis and showed significantly higher cell yield than controls. Further clinical studies are warranted.

References

DOI: 10.1053/j.gastro.2020.10.007
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DOI: 10.1038/ajg.2018.14
Mohamed, E.; et al. Role of radiological imaging in the diagnosis andcharacterization of pancreatic cystic lesions: a systematic review. Pancreas 2018, 47, 1055–1064.
Cazacu, I. M.; et al. A quarter cen- tury of EUS-FNA: Progress,milestones, and future directions. Endoscopic ultrasound 2018, 7, 141
DOI: 10.1038/s41598-021-81065-2
doi: 10.4103/eus.eus_93_17
Shirley, L. A.; et al. Routine cyst fluid cytology is not indicated in the evaluation of pancreatic cystic lesions. Journal of Gastrointestinal Surgery 2016, 20, 1581–1585.
Muniraj, T.; et al. Devices for endoscopic ultrasound-guided tissue acquisition. Techniques in Gastrointestinal Endoscopy 2018, 20, 2–9.
Balaban, V. D.; et al. EUS- through-the-needlemicrobiopsy forceps in pancreatic cystic lesions: A systematic review. Endoscopic Ultrasound 2021, 10, 19.
Marques, F.; et al. A loop-shaped minimally invasive brush for improved cytology sampling of pancreatic cysts during EUS-FNA. Medical Devices & Sensors 2021, 4, e10165.
doi: 10.1177/0271678X20943823.
doi: 10.3748/wjg.v18.i34.4659
DOI: 10.3748/wjg.v27.i26.4194

Disclosure

FM, WW, UA, NR, and FBS have patent applications for the brush technology and are co- founders of Lucky LoopMedical AB, a company commercializing technology for improved sampling in EUS-FNA. UA has received a research grant from Boston Scientific and is a consultant to Boston Scientific, Medtronic, and Ambu. IS declares no conflict ofinterest.

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]

Introduction

Preliminary data (PanCo) has suggested combined chemotherapy and endoscopic ultrasound (EUS) guided intra-tumoral phosphorus-32 (³²P) microparticles (OncoSil^TM Medical) may be beneficial in locally advanced pancreatic cancer (LAPC)¹. We report on the clinical outcomes in our Australia and New Zealand (ANZ) cohort with this combined therapy in LAPC.

Aims & Methods

This is a two-centre retrospective study from August 2017 – January 2023. All patients with non-metastatic unresectable or borderline resectable LAPC who underwent combination chemotherapy with EUS-guided intra-tumoral ³²P implantation were included from two centers in ANZ. First-line chemotherapy includes 5-fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine and nab-paclitaxel (GNP). Outcomes including 12-week response (RECIST 1.1), resection rate and overall survival were recorded and compared between FOLFIRINOX and GNP cohorts.

Results

A total of 49 patients (male:32; median age:72 years) underwent combined therapy (FOLFIRINOX:19, GNP:30). A median ³²P microparticle volume of 1mL (IQR 0.8-1.6) was injected into pancreatic tumors (median longest diameter:29.5mm (IQR 26.7-37)). Technical success of ³²P implantation was 100% with no acute complications. Local disease control in patients 12 weeks post-implant was 96%. Fifteen patients (31%; 26.3% of patients with FOLFIRINOX vs. 33.3% of patients with GNP, p=0.074) had tumor downstaging and were theoretically resectable whilst 9 (18.4%) had successful resections (6/9 R0). Two patients are awaiting resection, one patient opted not for surgery and three patients were deemed not fit for surgery. Over a median follow-up period of 20 months (range 3-67), 55% (27/49) have had disease progression (36% local progression, 42% distant progression). Median overall survival from diagnosis was 16 months (IQR 11-21; FOLFIRINOX=14.6 months vs. GNP=16.6 months, p=0.259).

Conclusion

This is the largest reported ANZ cohort with EUS-guided ³²P implantation for patients with LAPC. Additionally, this is the largest reported cohort of patients with combined therapy with FOLFIRINOX. The results of this current study are encouraging, forming a platform for larger trials and further ANZ involvement in investigating the benefits of combined therapy in patients with LAPC. Studies comparing standard therapy and combined chemotherapy with ³²P implantation are warranted.

References

1. Ross, P.J., et al., PanCO: An open-label, single-arm pilot study of phosphorus-32 (P-32; Oncosil) microparticles in patients with unresectable locally advanced pancreatic adenocarcinoma (LAPC) in combination with FOLFIRINOX or gemcitabine + nab-paclitaxel (GNP) chemotherapies. Journal of Clinical Oncology, 2019. 37(15_suppl): p. 4125-4125

Introduction

Colorectal cancer (CRC) screening is well established worldwide. However, the suboptimal sensitivity of the Fecal Immunochemical Test (FIT) for precancerous lesions justifies the search for new tools, namely microRNAs (miRs). In recent years, the detection of these molecules in liquid biopsies has gained increasing interest, as they reflect CRC progression and enable the early detection of precancerous lesions. Moreover, using miRs as a blood-based screening test could potentially increase patient adherence.

Aims & Methods

In this context, we aimed to identify circulating miR profiles for the early detection of CRC. Based on our previous literature review, we selected four miRs (miR-21-5p, miR-92a-3p, miR-451a and miR-199a-5p) with the best performance for the detection of CRC and high-grade dysplasia lesions (HGD). MiR expression was evaluated using RT-qPCR in plasma samples from 80 individuals who underwent colonoscopy with different clinical outcomes, namely, individuals without lesions found on colonoscopy, low-grade dysplasia lesions, high-grade dysplasia lesions, and patients diagnosed with CRC.

Results

Our findings demonstrate a decreased expression of all miRs in CRC and HGD lesions. Regarding HGD identification, miR-21-5p demonstrate a sensitivity of 68% (95% CI: 46 – 85%) and a specificity of 100% (95% CI: 84 – 100). Moreover, miR-92a-3p, miR-451a and miR-199a-5p demonstrated a sensitivity higher than 85% for HGD lesions detection, despite low sensitivity (around 70%). Concerning CRC detection, miR-92a-3p and miR-199a-5p demonstrated sensitivity of approximately 65%, with specificities of 70%, for miR-92a-3p (95% CI: 48 – 85%), and 80% for miR-199a-5p (95% CI: 58 – 92%). Furthermore, miR-21-5p showed outstanding performance in CRC identification with a sensitivity of 95% (95% CI: 75 – 100%), for an AUC of 0.900 (95% CI: 0.807 – 0.993). Moreover, when a negative result was obtained for one of these miRs, the presence of colorectal cancer lesions could be accurately excluded (negative predictive value: 98%).

Conclusion

These findings suggest that circulating miRs have the potential to improve the detection of precancerous lesions, surpassing the performance of FIT. Moreover, given their accuracy in identifying individuals without lesions, they could serve as effective confirmatory screening tools, reducing the number of unnecessary colonoscopies.
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