Clinical Case Summary

A 57- year- old female with past medical history of NF1 and diverticulitis presented with one day history of left lower quadrant abdominal pain, nausea, and vomiting. CT Abdomen and Pelvis demonstrated sigmoid diverticulitis without abscess, and an incidental mesenteric mass 4.4 x 3.1 x 3.7 cm in the left lower quadrant. She was medically managed with intravenous antibiotics and discharged five days later. She was scheduled for a 1 month follow up with general surgery, who recommended resection of the mass. She underwent a small bowel resection of the mass and was discharged on postoperative day three. Pathology was consistent with gastrointestinal stromal tumor with two foci, 5.4 cm, and 0.6 cm in size with negative margins. The overall mitotic index was low (2/50 HPF) with Ki-67 staining of 5%. Tumor cells were positive for CD117, DOG1, SMA and negative for CD 31, CD 34, MSA, S100 and Desmin. Onkosight NGS KIT sequencing revealed no clinically relevant mutations in KIT exons 2, 9, 10, 11, 13, 14, 15, 17 and 18. Oncology recommended CT surveillance scans every 6 months without adjuvant therapy since the tumor developed in the setting of NF1. Our patient unfortunately deferred routine screening due to loss of insurance and inability to afford the out-of-pocket costs of CT imaging. In summary, our case illustrates the rare occurrence of GIST in a patient with NF1. Since NF1-associated GISTs typically present in female patients in their fourth decade of life, our case highlights the importance of early screening. Surgical resection is the mainstay of treatment for this condition as seen in our patient while tyrosine kinase inhibitors are typically reserved for sporadic cases or those with high-risk features [1,2]. Thus, further research into cost effective diagnostic surveillance and non-surgical treatment modalities for those with NF1 associated GIST is warranted.

References

1. von Mehren M, Joensuu H. Gastrointestinal Stromal Tumors. J Clin Oncol. 2018 Jan 10;36(2):136-143. doi: 10.1200/JCO.2017.74.9705. Epub 2017 Dec 8. PMID: 29220298; PMCID: PMC6553810.
2. Rutkowski P, Skoczylas J, Wisniewski P. Is the Surgical Margin in Gastrointestinal Stromal Tumors Different? Visc Med. 2018 Oct;34(5):347-352. doi: 10.1159/000491649. Epub 2018 Aug 24. PMID: 30498701; PMCID: PMC6257087.

Introduction

Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) is one of the best imaging modalities to visualize tumor blood flow, but conventional observation can sometimes be insufficient, particularly in lesions characterized by rapid changes in blood flow. Inflow-time mapping (ITM) is a colored parametric display of time-to-peak enhancement for each pixel in the display that allows a better differentiation of tissues by their speed of contrast agent uptake. ITM is a simple, easily reproducible computer-aided color parametric imaging (CPI) technique that can bring a more objective approach to CEH-EUS analysis and further improve the differential diagnosis of pancreatic masses.

Aims & Methods

To investigate the potential advantages and limitations of Inflow-time Mapping - a novel computer-aided color parametric imaging technique - in assessing focal pancreatic lesions using contrast-enhanced harmonic endoscopic ultrasound.
A total of 15 patients including 8 cases of pancreatic ductal adenocarcinomas (PDAC), 3 cases of chronic pancreatitis, 2 cases of pancreatic neuroendocrine tumors (NETs), one case of serous cystadenoma (SCA) and one case of intraductal papillary mucinous neoplasm (IPMN) were enrolled. CEH-EUS and ITM examinations were performed for the frames obtained during the arterial phase. All CEH-EUS and ITM images were retrospectively reviewed and two sets of criteria were assigned: (1) Routine CEH-EUS alone, focusing on the degree and pattern of enhancement, and (2) CEH-EUS and ITM, focusing on differentiating pancreatic lesions based on their speed of ultrasound contrast agent (UCA) uptake, compared to adjacent tissue. Final diagnosis was based on EUS-guided tissue fine needle aspiration biopsy (EUS-FNAB).

Results

Based on CEH-EUS, 11 pancreatic lesions were initially considered PDAC based on their hypoenhanced appearance. ITM analysis could not provide additional information in 8 patients due to insufficient vascularization. In 3 patients, by showing no difference in the speed of UCA uptake in the enhanced regions of the lesion compared to the surrounding parenchyma, ITM analysis was able to correctly identify chronic pancreatitis, as proven by histology. Among the 2 hyperenhanced pancreatic lesions described on CEH-EUS, ITM analysis was able not only to correctly diagnose but also to provide an extensive characterization of 2 pancreatic NETs by showing a greater speed of UCA uptake in the lesion and a typical pattern of the parametric map. ITM analysis also proved useful in objectively highlighting the speed and pattern of enhancement (septal/mural) of 2 included cystic lesions, IPMN and SCA.

Conclusion

ITM is a promising tool for an objective, simplistic approach, in the assessment of hypervascular pancreatic lesions, particularly pancreatic NETs. It can also become an important step in the evaluation of focal pancreatic masses in patients with chronic pancreatitis, where parenchymal inhomogeneity and altered local perfusion might influence the purely visual assessment of CEH-EUS.

References

Dietrich CF, Dong Y, Froehlich E, Hocke M. Dynamic contrast-enhanced endoscopic ultrasound: A quantification method. Endosc Ultrasound. 2017 Jan-Feb;6(1):12-20. doi: 10.4103/2303-9027.193595. PMID: 28218195; PMCID: PMC5331837

Clinical Case Summary

A 45-year-old woman was founded with a raised serum alpha-fetoprotein (AFP) level of 89 ng/ml ( normal range < 8ug/L ) when taking a routine physical examination. During the following year, the serum AFP concentration level was gradually rising, up to 6353 ng/ml. There was no significant loss of weight or loss of appetite, and she denied having any feeling of bloating or abdominal pain.
Although the serum AFP concentration level was abnormally high, the cancer antigen (CA)125, cancer antigen (CA)199, carcinoembryonic antigen (CEA), PIVKA-II, AFP-L3, β-HCG levels were all within normal limits at each check. There was no abnormal findings in the hepatobiliary systems except the modest increased bilirubin (within 2 times). Hepatitis A, hepatitis C, hepatitis E antibody screen was negative. The result of HBV markers were: HBsAg(-), HBsAb(+), HBeAb(-), HBeAb(-), HBcAb(+), While HBV DNA quantification was less than 5.00E+2 IU/ml. Moreover, there was no significant abnormality concerning autoimmune liver disease. During the one-year follow up, several imaging examinations were performed,including abdominal ultrasonography, enhanced computer tomography (CT) , magnetic resonance imaging (MRI) and PET-CT. However, there was no evidence of liver lesion or tumour on all of them, even the PET scan.To check for hepatoid adenocarcinoma, gastroscopy, colonscopy, enhanced chest CT enhanced abdomen CT, and thyroid ultrasound were performed. Nevertheless, no suspicious lesion was found.
One year later, a 2.8×2.6 cm mass was detected in the left lobe of liver in a surveillance ultrasound scan. She underwent laparoscopic hepatocarcinoma resection, and the mass was confirmed moderately differentiated hepatocellular carcinoma by pathology. After surgery, AFP levels took 3 months to normalize.
From this case, we found that a gradual rise elevation in AFP were positive predictors for tumor development, especially hepatocellular carcinoma.

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

Diverticular disease of the colon is one of the most common diseases in Western world. Despite in the natural history in most of cases diverticulosis remains asymptomatic or manifests with mild abdominal pain, complications may occur. Bleeding from diverticula is one of the most common complications and, despite it is usually a self-limiting event, it may lead to anemia or shock. Among the endoscopic interventions for active bleeding, direct or indirect clipping of the diverticulum is the most diffuse one. However, it has been hypothesized that endoscopic band ligation (EBL) may be more effective, since it may improve the chance to close the bleeding vessel, with a better outcome on long term. Therefore we performed a meta-analysis comparing clipping versus EBL for diverticular bleeding.

Aims & Methods

Literature search on main databases (PubMed, Web of science, SCOPUS, EMBASE) was performed in November 2022. Studies comparing clip versus EBL for acute diverticular bleeding were selected. We excluded case series, abstract and articles not written in English. The following outcomes were analysed: short term effectiveness, early rebleeding, tardive rebleeding and need for surgery or radiologic embolization. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculate according to Mantel-Haenszel method. Heterogeneity was estimated by I² statistic with chi square test, and, if present, a random effect model was used, otherwise a fixed one was adopted.

Results

Seven studies were selected, overall enrolling 2322 patients (979 in EBL and 1343 in clip groups). Immediate haemostasis was achieved in the EBL and clipping group respectively in the 96.8% and 96.5% (OR=0.94, 95% CI 0.59-4.19, p=0.79). Early rebleeding was observed more frequently in the clipping (25.0%) than in the EBL group (11.8%), with an OR=0.40 (95% CI 0.32-0.51, p<0.001). Similarly, tardive rebleeding was more common in the clipping arm (37.4%) than in the EBL (24.5%), OR=0.39, 95% CI 0.22-0.68, p=0.0001. Patients receiving clipping needed more frequently salvage surgery or embolization than EBL (1.48% versus 0.53%, OR=0.40, 95% CI 0.17-0.93, p=0.03).

Conclusion

Despite EBL and clip have similar effectiveness in achieving immediate haemostasis, EBL showed better effectiveness in maintaining it on longer interval times, with less probable need for major surgical/radiologic interventions.

Introduction

Colonic diverticular bleeding (CDB) is the most common cause of acute lower gastrointestinal bleeding (ALGIB) and often requires blood transfusion. There are several studies regarding the use of restrictive blood transfusion for acute upper gastrointestinal bleeding, but there is only one previous study regarding the use of restrictive blood transfusion for ALGIB [1]. Therefore, the efficacy of restrictive blood transfusion for CDB remains unclear.

Aims & Methods

This study sought to elucidate the association between the restrictive blood transfusion strategy and the clinical outcomes in patients with CDB. We retrospectively analyzed 475 patients who were urgently hospitalized for CBD and received blood transfusions at two facilities between November 2013 and December 2021. Transfusion strategy was defined as the restrictive group when patients received transfusion for hemoglobin (Hb) ≤ 7 g/dl, and the liberal group when patients received for Hb > 7 g/dl. The hemoglobin cut-off value for restrictive blood transfusion was determined based on a prior randomized clinical trial regarding UGIB [2]. Rebleeding within 30-days, mortality within 30-days, and composite outcome within 30-days were evaluated. The composite outcome comprised the following endpoints: rebleeding, need for surgery or IVR for hemostasis, and mortality within 30 days. We also investigated medical costs during hospitalization. Logistic regression analysis was performed to calculate the odds ratios (OR) with 95% confidence interval (CI) to analyze associations between restrictive transfusion strategy and outcomes.

Results

Of 475 patients, 184 (38.7%) (124 males, 60 females, mean age 76.5±11.5 years) patients received blood transfusion. The mean hemoglobin levels at the time of transfusion in the restrictive and liberal groups were 6.3±0.6 g/dl and 8.2±1.2 g/dl, In the restrictive and liberal group, rebleeding within 30-days was 53.9% and 45.3% (P = 0.24), the mortality within 30-days was 1.1% and 0% (P = 0.30), the composite outcome within 30-days was 56.1% and 52.6% (P = 0.63), respectively. After adjusting for potential confounders, multivariate analysis revealed that restrictive transfusion strategy not associated with decreased rebleeding risk within 30-days, (P = 0.42 ; odds ratio [OR], 1.3), whereas endoscopic hemostasis significantly associated with decreased rebleeding risk (P < 0.01 ; OR 0.2). There was no statistically significant difference in total medical costs between the two groups (P = 0.68).

Conclusion

There were no statistically significant differences in rebleeding within 30-days, mortality within 30-days, and compositeoutcome within 30-days between the restrictive and liberal blood transfusion strategies. Restrictive blood transfusion may be a reasonable therapeutic strategy for patients with CDB, except for patients in which shock status cannot be withdrawn. However, further evidence is needed to advocated the efficacy of restrictive transfusion strategies for lower gastrointestinal bleeding.

References

[1] Kherad O, Restellini S, Martel M, Sey M, Murphy MF, Oakland K, et al. Outcomes following restrictive or free red blood cell transfusion in patients with lower gastrointestinal bleeding. Aliment Pharmacol Ther. 2019 Apr;49(7):919–25.
[2] Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan;368(1):11–21.