Clinical Case Summary

Meckel's diverticulum, affecting around 2% of the population, is more common in men and typically presents before age two. The lifetime risk of complications, including gastrointestinal bleeding, is about 4%. Symptomatic cases during pregnancy are rare, with only 38 documented since 1949. A unique case of gastrointestinal bleeding in the second trimester is reported.
Case report: An 18-year-old female in her 19th week of pregnancy presented at the hospital with multiple black stools, dizziness, and severe pallor. Initial tests showed a hemoglobin level of 4.5 g/dL, prompting a transfusion that raised it to 9.5 g/dL. An endoscopy revealed no bleeding lesions, and a colonoscopy was incomplete due to abundant clots. An abdominal angiotomography indicated a reduction in the middle ileum caliber. Surgery revealed a Meckel's diverticulum,an intestinal resection with end-to-end ileal anastomosis was performed.Histopathology confirmed ectopic gastric mucosa within the diverticulum
Meckel's diverticulum, commonly called “the great simulator,” exhibits a range of non-specific symptoms that make diagnosis challenging, particularly during pregnancy when imaging choices are restricted.If required, CT scans and radiography can be utilized as long as radiation exposure remains under 100 mGy, given that standard CT scans are typically below 50 mGy. From a histological standpoint, Meckel's diverticulum is similar to the ileum; however, ectopic gastric tissue can be present in 12-26% of cases, leading to issues such as ulceration and bleeding,this is thought to result from alterations in the local intestinal environment due to the secretion of hydrochloric acid, pepsin, and other endogenous factors by the ectopic tissue.The importance of this case is that symptomatic Meckel's diverticulum during pregnancy is rare, with only a few case reports documented.

References

Figure 1. Angiotomography showing hyperenhancement, venous engorgement and reduction in the caliber of a segment of the middle ileum.
Figure 2. Intra-operative finding Meckel’s diverticulum.
Figure 3. Photomicrograph showing diverticular wall composed of oxyntic gastric mucosa. H&E stain (x5).

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2. Féria, B., Trindade, M., Palma, M. J., Figueiredo, J., & Passos, F. (2022). Meckel's Diverticulum: The "Great Mimic" but Often a Forgotten Cause of Acute Abdomen during Pregnancy. Case reports in obstetrics and gynecology, 2022, 2383075. https://doi.org/10.1155/2022/2383075
3. Sima, R. R., Rajan, C. S., & Aithal, S. K. (2016). Bleeding Meckel’s in pregnancy: A rare cause of a rare phenomenon. Surgical science, 07(02), 96–99. https://doi.org/10.4236/ss.2016.72013
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Clinical Case Summary

Introduction: Hepatic Epithelioid Hemangioendothelioma constitutes an uncommon neoplasm that come up from vascular entities. The liver is identified as the predominant primary site. A histopathological assessment is essential for the accurate diagnosis. Liver transplantation has been acknowledged as a viable treatment modality for hepatic EHE; however, concerns about its effectiveness persist, predominantly due to the risk of disease recurrence after transplantation and the typically indolent behavior of the tumor.
Case Report: A 29-year-old female patient had a medical history of liver transplantation occurring at the age of 19 due to epithelioid hemangioendothelioma, diagnosed when she was 15 years old. Thirteen years following the transplantation, she began experiencing abdominal pain. On June 2, 2024, a CT angiogram was conducted, revealing a pathological enlargement of the superior mesenteric vein that extended into the intrahepatic portal vein. A liver ultrasound was performed on June 12, 2024, indicated early signs of chronic liver disease and identified a nodule situated in segment VIII of the liver. Subsequently, a triphasic liver CT scan carried out on June 24, 2024, illustrated an irregular texture along with multiple nodules exhibiting decreased density. Furthermore, a CT angiogram was performed on July 19, 2024, demonstrated numerous nodular lesions within the peripheral areas of the liver. A liver Doppler ultrasound was performed on August 26, 2024, revealed several focal lesions within the liver graft, which may indicate a potential recurrence of the initial condition, epithelioid hemangioendothelioma.
Conclusions: Multiple factors, including the patient's age at diagnosis and tumor dimensions, have been associated with unfavorable prognostic outcomes. Recurrence typically occurs approximately 49 months post-treatment; however, it may manifest as late as 12 years following liver transplantation.

References

1. Ajay, P.S., Tsagkalidis, V., Casabianca, A., et al. A review of hepatic epithelioid hemangioendothelioma—Analyzing patient characteristics and treatment strategies.
Journal of Surgical Oncology, 2022;126(8):1423-1429. DOI: 10.1002/jso.27066
2. Xu, J., Hu, S., Li, S., et al. Laparoscopic resection of hepatic epithelioid hemangioendothelioma: report of eleven rare cases and literature review. World Journal of Surgical Oncology, 2020;18:282. DOI: 10.1186/s12957-020-02034-z
3. Liu, X., Yang, P., Liu, L., Si, S., Zhou, R., Liu, T., & Tan, H. (2024). Long-term prognosis and treatment modalities of hepatic epithelioid hemangioendothelioma: a retrospective study of 228 patients. BMC Cancer, 24(1). https://doi.org/10.1186/s12885-024-13053-4
4. Tan, H., Zhou, R., Yu, H., Teng, F., Si, S., Liu, L., Yang, S., Han, D., & Liu, X. (2023). CT appearances and classification of hepatic epithelioid hemangioendothelioma. Insights Into Imaging, 14(1). https://doi.org/10.1186/s13244-023-01410-z

Introduction

Percutaneous endoscopic gastrostomy (PEG) is recommended for long-term enteral nutrition in dysphagic patients with a vast heterogeneous group of underlying conditions. Decision-making for gastrostomy placement requires careful consideration on a case-by-case basis, with the underlying condition, clinical status and prognosis taken into account. Although estimating prognosis is a critical factor in the decision-making of PEG tube placement, it remains challenging and heavily reliant on clinical judgement.

Aims & Methods

Retrospective study of adult patients who underwent PEG in a tertiary hospital from 2001 to 2023. This study aims to characterize conditions motivating PEG, assess nutritional status on the gastrostomy day, evaluate survival and search for survival predictors. Data collected included demographics, underlying disorders, nutritional status (anthropometry/laboratory evaluation) on the day of PEG and survival recorded until death or December 2023. Multivariable analysis was performed with Cox regression to search for survival predictors.

Results

A total of 1415 patients were included (61.8% males, mean age 66.9 years); 66.4% presented a neurological disorder (35.3% with a potentially regressive course and 31.2% with a progressive course) and 31.3% head and neck or esophageal cancers (HNC/EC). The most frequent underlying conditions were post-stroke dysphagia (25.5%), dementia (11%) and amyotrophic lateral sclerosis (10.8%). The mean BMI was 20.9 kg/m2, with 49.8% underweight patients. Albumin, transferrin and total cholesterol were low at 43.2%, 62.2% and 50%, respectively. Median overall survival was 11.1 months, with a 1-, 3- and 5-year survival rates of 48.2%, 27.8% and 19.6%, respectively. 14.1% of deaths occurred within 4 weeks. These short survivors were significantly older and had lower mean albumin, transferrin and total cholesterol levels. Although BMI was also lower, this difference did not reach statistical significance. Potentially regressive neurological conditions presented higher survival than progressive ones (16.6 vs. 13.3 months, p = 0.004). HNC/EC patients presented a significantly lower survival (6.6 months) when compared to both of these groups (p < 0.001). Besides underlying condition, predictors of increased survival on the multivariable analysis included female gender (HR 0.396), younger age (HR 0.980), higher albumin (HR 0.687) and higher BMI (HR 0.963). The protective effect of BMI and albumin was more pronounced in males than in females.

Conclusion

Neurological disorders were the most frequent underlying conditions. Nearly half of the patients displayed malnutrition before PEG feeding. Although PEG-fed patients displayed a considerable median survival time, some died early without benefit from PEG. Patients with potentially regressive neurological conditions presented better outcomes. Female gender, younger age, higher albumin and higher BMI were associated with longer survival. The findings emphasize the complex interplay of clinical, demographic and nutritional factors influencing survival after PEG tube placement. By integrating these predictors of survival into clinical practice, patient selection can be tailored in order to optimize outcomes.

Introduction

Immune checkpoint inhibitors (CPI) have revolutionised cancer outcomes, but frequently trigger immune related adverse effects, including life-threatening colitis. Tissue resident memory (TRM) T cells are key cells involved in the pathogenesis of CPI-induced colitis (CPI-C), but the mediators they produce to facilitate disease are poorly defined.

Aims & Methods

We utilised our previously published in vivo pre-clinical model of CPI-C, which occurs when mice are given combination anti-CTLA4 and anti-PD1 and a proinflammatory microbiota mix, to define the role of the Granzyme A/B cytotoxicity pathway in disease. Disease was induced in wildtype (WT) and Granzyme A/B double knockout (GzmAB^-/-) mice. Clinical outcomes (colon and spleen mass, histology and infiltrating neutrophils) from these mice were assessed to measure the severity in disease. T cell populations were also analysed using flow cytometry.

Results

GzmAB^-/-mice showed a significant reduction in disease features compared to WT mice, with reduced colon mass, reduction in infiltrating neutrophils and fewer inflammatory monocytes. Flow cytometry analysis of the T cell compartment revealed a significant reduction in both bulk CD4 and CD8 T cells and also CD4 and CD8 tissue resident memory T cells in both the cLP and IEL in GzmAB^-/-mice treated with CPI-C in comparison to WT mice treated with CPI-C. GzmAB^-/-mice treated with CPI-C also had a reduction in IFNγ and TNFα production from both CD4 T cells and CD8 T cells. These data highlight the importance of granzymes in inducing the disease phenotype in CPI-C. In order to investigate whether CD4 T cells or CD8 T cells were more important, we depleted these cells in vivo in WT mice treated with CPI-C at both 1 and 3 weeks. Here, we found that WT mice with CD4 T cells depleted got significantly worse disease with colon masses increasing and there being increased infiltrating neutrophils. There was an increase in cytotoxic cytokines being produced by CD8 T cells when CD4 T cells were depleted. However, when CD8 T cells were depleted, there was no change in any clinical features or cytokine production from CD4 T cells.

Conclusion

Using GzmAB^-/- mice we have demonstrated that CPI-colitis is at least partially dependent on the granzyme cytotoxicity pathway. Targeting the cells that produce granzyme in the colon of patients with CPI-colitis might offer an attractive novel treatment option for patients with CPI-colitis.

References

1. Lo, J.W., Cozzetto, D., Alexander, J.L. et al. Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNγ axis. Nat Commun 14, 6719 (2023). https://doi.org/10.1038/s41467-023-41798-2
2. Luoma A. M. et al. Molecular pathways of colon inflammation induced by cancer immunotherapy. Cell 182, 655-671.e22 (2020).
3. Sasson, S. C. et al. Interferon-gamma-producing CD8(+) tissue resident memory T cells are a targetable hallmark of immune checkpoint inhibitor-colitis. Gastroenterology 161, 1229–1244.e1229 (2021).
4. Gupta T, Antanaviciute A, Hyun-Jung Lee C, et al. Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis. Cancer Cell. 2024 May 13;42(5):797-814.e15. doi: 10.1016/j.ccell.2024.04.010. PMID: 38744246.