Introduction

Pancreatic acinar cystic transformation (ACT) was first described in 2000. Its initially supposed pre-neoplastic nature was reconsidered in the WHO Classification 2019. Its current management prone to a non-surgical approach, and so rare cases of histopathological diagnosis have been obtained since. Radiological diagnostic criteria have been proposed to differentiate ACT from Branch-duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN) (Delavaud et al., 2014): 1) ≥ 5 cysts, 2) clustered peripheral small cysts, 3) cyst calcifications and 4) no communication with the main pancreatic duct.

Aims & Methods

The aims of this study were to describe the clinical and radiological characteristics of patients with a presumed diagnosis of ACT in imaging and to assess the role of these known radiological criteria in case of possible differential diagnoses. In this single-centre retrospective study (2003-2021), consecutive patients with a presumed diagnosis of ACT in the coding database were included. Patients without an available imaging (CT or MRI) for expert radiological centralized review were excluded. A group of “typical” diagnosis of ACT was defined as the absence of differential diagnosis to be evoked. A group of “uncertain” diagnosis of ACT was defined as other possible differential diagnoses.

Results

A total of 64 patients were included (35 male patients [55%]). Median age of diagnosis was of 60 (IQR 47-67) years. ACT diagnosis was “typical” for 35 (55%) patients and was “uncertain” for 29 (45%) patients. In the “typical” group, 91.4% of patients presented ≥3 radiological criteria versus 96.6% in the “uncertain” group (p=0.61). There were more calcifications and <10 cysts in the “uncertain” group compared to the “typical” group (86% versus 66%, p = 0.041 et 24% versus 6%, p = 0.06, respectively). In the “uncertain” group, the main differential diagnoses suggested were: 16 (55%) BD-IPMN and 7 (24%) calcified chronic pancreatitis (CCP). A pathological confirmation of ACT was obtained for three patients from which two were in the “uncertain” group.

Conclusion

ACT displays an heterogenous morphological imaging presentation reflecting a challenge for accurate non-invasive diagnosis. The published diagnostic radiological criteria seem not to be sufficient, especially in case of calcifications or/and <10 cysts.

References

Delavaud C, d’Assignies G, Cros J, et al. CT and MR imaging of multilocular acinar cell cystadenoma: comparison with branch duct intraductal papillary mucinous neoplasia (IPMNs). Eur Radiol 2014; 24: 2128–2136

Disclosure

No conflict of interest to be disclosed

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

The randomized controlled OPTIC trial reported that optimised mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at one year in ulcerative colitis (UC) patients failing 5-aminosalicylates after receiving induction treatment with corticosteroids.

Aims & Methods

We aimed to assess cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment in UC. Data were collected during the OPTIC trial to perform a health economic evaluation for mercaptopurine treatment versus placebo in UC patients. The economic evaluation was performed from a health care and societal perspective using a cost-effectiveness and cost-utility analysis with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. Main outcomes were the costs per patient who achieved combined corticosteroid-free clinical remission and endoscopic improvement at one year and the costs per quality-adjusted life-year (QALY).

Results

In total, 59 patients were randomized to the intervention (n = 29) and control (n = 30) group. Patients on mercaptopurine treatment showed a non-significant gain in QALYs of 0.047 (-0.024 to 0.117) (P=0.184) corrected for baseline health utility. Non-significant differences in costs were €63 (-€1267 to €1434; P=0.927) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P=0.644) in favour of mercaptopurine from a societal perspective, including patients’ out-of-pocket expenses and employers’ productivity loss. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000.

Conclusion

Optimised mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.

References

1. de Boer NKH, Peyrin-Biroulet L, Jharap B, et al. Thiopurines in inflammatory bowel disease: new findings and perspectives. J Crohns Colitis 2018;12:610–20.
2. Löwenberg, M., Volkers, A., van Gennep, S., Mookhoek, A., Montazeri, N., Clasquin, E., Duijvestein, M., van Bodegraven, A., Rietdijk, S., Jansen, J., van Asseldonk, D., van der Zanden, E., Dijkgraaf, M., West, R., de Boer, N., & D'Haens, G. (2023). Mercaptopurine for the Treatment of Ulcerative Colitis: A Randomized Placebo-Controlled Trial. Journal of Crohn's & Colitis, 17(7), 1055–1065.

Disclosure

NA

Introduction

Biliary stenting by endoscopic retrograde cholangiopancreatography (ERCP) is a common palliative endoscopic procedure for unresectable malignant biliary obstruction or for patients unfit for surgery.

Aims & Methods

We conducted a multicentre retrospective cohort study in 3 centres in Portugal, involving patients submitted to first palliative biliary drainage for malignant biliary obstruction by ERCP, between 2015 and 2022. This study aimed to identify predictive factors of 90-day mortality after endobiliary drainage and propose a predictive model. We have analysed data from 217 patients. Statistical analysis was performed using SPSS v.29.

Results

In our cohort, 51,2% (N=111) of patients were female and the mean age was 74 years. 52,5% (N=114) had stage IV disease and in 88% (N=191) the biliary obstruction resulted from primary tumour involvement. The most frequent tumour was primary pancreatic cancer (53,5%, N=116), followed by cholangiocarcinoma (26,7%, N=58). Metallic stents were used in 53,9% (N=117) of the patients, mainly with fully uncovered self-expandable metallic stents (66,7%, N=78). In the multivariate regression model, the independent predictors for 90-day mortality after first ERCP-guided stent placement were primary tumour size <3 cm (p = 0,014; OR 0,394; 95% CI, 0,187-0,830), stage IV malignant disease (p = 0,005; OR 3,776; 95% CI, 1,507-9,465), intrahepatic biliary obstruction (p = 0,004; OR 3,727; 95% CI, 1,518-9,150) and palliative chemotherapy after ERCP biliary drainage (p <0,0001; OR 0,44; 95% CI, 0,015-0,132). Using these variables, we developed a prediction model for the risk of mortality within 90 days after biliary drainage (Hosmer-Lemeshow X² = 2,907, p = 0,893) with R² of 44,1% in our cohort. The AUROC for our prediction model was 0,833 (p <0,0001; 95% CI, 0,774-0,892). By the Youden’s J statistic, the optimal cut-off value for was 0,4, with a sensitivity of 73,9% and specificity of 76,3%. Patients with a score < 0,2 had a low likelihood of death, whereas a score ≥ 0,9 had a high likelihood of death.

Conclusion

The present study was able to identify statistically significant predictive factors of 90-day mortality after ERCP-guided biliary stenting in unresectable malignant biliary obstruction, which may help to stratify the risk of death within 90 days post-stent placement. Since all these predictive factors can be determined before ERCP, this risk stratification could help in the definition of the proper palliative strategy for each patient.

References

Termsinsuk, P., Charatcharoenwitthaya, P., & Pausawasdi, N. (2022). Development and validation of a 90-day mortality prediction model following endobiliary drainage in patients with unresectable malignant biliary obstruction. Frontiers in oncology, 12, 922386. https://doi.org/10.3389/fonc.2022.922386;
Sripongpun, P., Attasaranya, S., Chamroonkul, N., Sookpaisal, T., Khow-Ean, U., Siripun, A., Kongkamol, C., Piratvisuth, T., & Ovartlarnporn, B. (2018). Simple Clinical Score to Predict 24-Week Survival Times in Patients with Inoperable Malignant Distal Biliary Obstruction as a Tool for Selecting Palliative Metallic or Plastic Stents. Journal of gastrointestinal cancer, 49(2), 138–143. https://doi.org/10.1007/s12029-017-9918-9;
Afshar, M., Khanom, K., Ma, Y. T., & Punia, P. (2014). Biliary stenting in advanced malignancy: an analysis of predictive factors for survival. Cancer management and research, 6, 475–479. https://doi.org/10.2147/CMAR.S71111.

Clinical Case Summary

A 72 years old caucasian women with no relevant medical history presented to the emergency department with two weeks history of abdominal pain in the upper quadrants associated with fullness, vomiting and a significant weight loss and nighttime hypersweating. On physical examination, abdomen was painful on epigastric and periumbilical region. Analytically, hemoglobin 11.1g/dL, leukocytes 9200/mm3, platelet count 315000/μL, CRP 8.22mg/dL. Tests for HIV and EBV were negative. Computed Tomography (CT) of the abdomen and pelvis revealed stomach with thickened walls, densification of adjacent fat and heterogeneous adenopathies. She was admitted to the department of Gastroenterology for investigation. The upper gastrointestinal endoscopy revealed extensive neoplasia of the body and gastric antrum. Biopsies revealed gastric mucosa with infiltration by atypical lymphoid proliferation with a "starry sky" pattern suggestive of high-grade B-cell non-Hodgkin's lymphoma (NHL). FISH analysis revealed t(8;14) c-myc positive. Once morphological and immunohistochemistry feature favors Burkitt’s lymphoma, she was transferred to the department of Hematology. Patient was treated with a full dose CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) and 3 cycles of dose adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab). Complete remission was documented on positron emission tomography (PET).
Sporadic Burkitt's lymphoma is rare (1-2% of all lymphomas in adults), being one of the most aggressive forms of B-cell NHL. Primary gastric involvement is extremely rare. With the advancement of medicine and greater survival, we must consider this diagnosis, even in the absence of risk factors, atypical location and age group. This case emphasizes the importance of clinicopathological correlation and the importance of early diagnosis for immediate and aggressive intervention, fundamental in reducing morbidity and mortality.

References

1. Zhimin Bai, Yong Zhou. A systematic review of primary gastric diffuse large B-cell lymphoma: Clinical diagnosis, staging, treatment and prognostic factors, Leukemia Research,
Volume 111, 2021, 106716, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2021.106716.
2. Čubranić A, Golčić M, Fučkar-Čupić D, Brozović B, Gajski D, Brumini I. BURKITT LYMPHOMA IN GASTROINTESTINAL TRACT: A REPORT OF TWO CASES. Acta Clin Croat. 2019 Jun;58(2):386-390. doi: 10.20471/acc.2019.58.02.25. PMID: 31819338; PMCID: PMC6884372.
3. Usman A. Pirzada, Kishore Kumar, Hassan Tariq, Masooma Niazi, Jasbir Makker; Case of Gastric Diffuse Large B-Cell Lymphoma. Case Rep Oncol 6 May 2019; 12 (1): 39–46. https://doi.org/10.1159/000496332
4. Khan A, Khan S, Arshad U. Primary Gastric Burkitt's lymphoma. Pak J Med Sci. 2017 Sep-Oct;33(5):1294-1297. doi: 10.12669/pjms.335.13002. PMID: 29142583; PMCID: PMC5673752.

Introduction

The incidence of elderly-onset ulcerative colitis (EO-UC) and Crohn’s disease (EO-CD) is increasing globally. However, whether the initial disease presentation of EO-UC and EO-CD differs from that in adult-onset (AO) is currently poorly investigated.

Aims & Methods

The aims of this study were to explore the initial presentation, severity, and disease course of newly diagnosed EO-UC and EO-CD (age ≥60 years) in comparison to AO-UC and AO-CD (18–59 years). The study was conducted as an ongoing prospective population-based inception cohort, IBD Prognosis Study, with enrollment between May 2021 and April 15^th, 2023, within a catchment population of 1.050.000 citizens (~20% of the Danish population). We defined severe disease course as requiring surgery or initiation of biological therapies within six months of diagnosis.

Results

The cohort comprised 501 patients, including 398 (79.4%) with AO disease (AO-UC: 223 (56.0%), AO-CD: 145 (36.4%), AO-IBDU: 30 (7.5%)), and 99 (19.8%) with EO disease (EO-UC: 64 (64.6%), EO-CD: 35 (35.4%), EO-IBDU: 5 (5.1%)). A comparison of the clinical presentation, severity, and initial disease course is presented in Table 1. As shown, EO-UC and EO-CD did not differ significantly from AO-UC and AO-CD in terms of demographic factors, disease phenotype, severity, and initial therapy. However, a significantly higher proportion of patients with EO-UC had left-sided UC, and tended to be treated less frequently with biological therapies and immunomodulators.
In a Cox multivariable regression model with Bonferroni correction adjusting for disease type and gender, patients with EO-UC (adjusted hazard ratio (aHR)=1.9 (95% confidence interval (CI) 0.5-7.3)) and EO-CD (aHR =4.1 (95% CI 0.3-12.3)) were not at different risk of requiring surgery or initiation of biological therapies within six months of diagnosis than patients with adult-onset IBD.
Table 1: Pairwise comparison of newly diagnosed elderly-onset and adult-onset inflammatory bowel diseases

Conclusion

In this population-based study, we found no difference between EO-IBD and AO-IBD in terms of initial disease presentation, severity, and course. However, patients with EO-IBD tended to be treated with less biological therapies and immunomodulators.

Disclosure

Mohamed Attauabi: None
Gorm Roager Madsen: None
Flemming Bendtsen: Tillotts, Ferring
Klaus Theede: Ferring, Janssen, Takeda, Pfizer, and Tillotts
Jakob Benedict Seidelin: has received research grants from Takeda, Janssen and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. None of these pertain to the research submitted here.
Johan Burisch: reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.

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.