Drug-induced Pancreatic Atrophy (“The Vanishing Pancreas”)

Iyad Khamaysi¹,²https://orcid.org/0000-0001-9642-2758, Eisa Hajj²

¹The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

²Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel

Corresponding Author: Iyad Khamaysi, Department of Gastroenterology, Endoscopy Unit, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel, Phone: +972 4 777 2850, Fax: +972 4 777 3058, e-mail: k_iyad@rambam.health.gov.il, k_iyad@technion.ac.il, iyad.khamaysi@gmail.com

How to cite this article: Khamaysi I, Hajj E. Drug-induced Pancreatic Atrophy (“The Vanishing Pancreas”). Euroasian J Hepato-Gastroenterol 2020;10(2):101–102.

Source of support: Nil

Conflict of interest: None of the authors has a COI to declare. This manuscript has not been presented before

ABSTRACT

Immune checkpoint inhibitors have become the therapeutic mainstay in a rapidly growing number of cancers. Immune checkpoint inhibitor-related diarrhea is attributed mainly to inflammatory colitis, with no other drug-related differential diagnosis. However, other causes of diarrhea should be considered. Pancreatic atrophy (and exocrine pancreatic insufficiency) is a relatively rare complication of immune checkpoint inhibitors. Herein we bring a set of striking computed tomography (CT) images that demonstrate a drug-related-progressive pancreatic atrophy until complete vanishing of pancreatic tissue. Exocrine pancreatic insufficiency (EPI) was diagnosed. Pancreatic enzyme replacement therapy was initiated with an excellent clinical response.

Keywords: Atrophy, Chemotherapy, Pancreas.

A 60-year-old female with metastatic renal cell carcinoma was referred to the gastroenterology department for diarrhea and weight loss.

About 6 months before presentation, the patient started to suffer from progressive back pain. After a short workup, renal cell carcinoma with bone metastasis was diagnosed. Immunotherapy with a combination of two checkpoint inhibitors (anti-CTLA-4 [ipilimumab] and anti-PD-1 [nivolumab]) was started.

Three months later, worsening steatorrhea appeared.

Physical examination was unremarkable.

Laboratory tests including lipase, amylase, liver enzymes, and IGG4 levels were normal.

Fecal elastase-1 levels were markedly reduced (57 µg/g stool).

Endoscopic workup was normal including gastric, duodenal, ileal, and colonic biopsies.

Serial positron emission tomography–computed tomography (PET-CT) scans before and after the immunotherapy showed progressive pancreatic atrophy. Six months after the initiation of the therapy, complete vanishing of pancreatic tissue was observed (Fig. 1, panels A–C).

Exocrine pancreatic insufficiency (EPI) was diagnosed. Pancreatic enzyme replacement therapy was initiated with an excellent clinical response.

Immune checkpoints are proteins that control immune cell activation.

Agents blocking the PD-1 axis (anti-PD-1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, avelumab, and durvalumab) have become the therapeutic mainstay in a rapidly growing number of cancers.¹

Immune checkpoint inhibitor-related diarrhea is attributed mainly to inflammatory colitis. However, other causes of diarrhea should be considered.²

Checkpoint inhibitor-induced pancreatic atrophy is irreversible and can result in EPI.

Fig. 1: Serial PET-CT scans before and after the immunotherapy showed progressive pancreatic atrophy

Exocrine pancreatic insufficiency should be suspected in patients treated with checkpoint inhibitors who are suffering from steatorrhea. EPI symptoms are largely responsive to pancreatic enzyme supplements.³

ORCID

Iyad Khamaysi https://orcid.org/0000-0001-9642-27581

REFERENCES

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2. Champiat S, Lambotte O, Barreau E, et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol 2016;27(4):559–574. DOI: 10.1093/annonc/mdv623.

3. Eshet Y, Baruch EN, Shapira-Frommer R, et al. Clinical significance of pancreatic atrophy induced by immune-checkpoint inhibitors: a case-control study. Cancer Immunol Res 2018;6(12):1453–1458. DOI: 10.1158/2326-6066.CIR-17-0659. Epub 2018 Oct 1. PubMed PMID: 30275274.

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