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Subacute Abdominal Pain in a Patient With Chronic Liver Disease and Hepatocellular Carcinoma

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 66-year-old woman with chronic hepatitis B infection and hepatocellular carcinoma (HCC) presented with subacute epigastric pain. Three years prior, she was diagnosed with a solitary HCC and underwent surgical resection with curative intent. Pathology revealed poorly differentiated HCC, 16 cm in largest dimension, with large vein involvement (T3bNXM0, R0 resection). The patient underwent expectant observation. One and a half years prior to the current presentation, laboratory results revealed an elevated α-fetoprotein (AFP), and cross-sectional imaging revealed multiple lung nodules consistent with metastases. She was treated with nivolumab every other week and attained a biochemical (baseline, 212.2 ng/dL; best response, 3.3 ng/dL) and radiographic complete response.

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B. Immunotherapy-related gastritis

This case highlights an increasingly common circumstance encountered in the management of patients with advanced liver cancer as well as other solid tumors—diagnostic considerations for an acute medical issue in a patient with a long-term response to ongoing immunotherapy.1,2 Here, the patient had been receiving treatment for 18 months without evidence of active liver cancer and presented with epigastric pain, a common clinical complaint with a broad differential diagnosis.3 The evaluation must consider the presence of chronic liver disease and metastatic HCC, as well as the potential complications of immunotherapy.

As the median progression-free survival with metastatic HCC being treated with frontline immunotherapy is only 3.7 to 6.8 months, worsening abdominal pain warrants immediate assessment for progressive cancer.1,2 Normal AFP level and atypical imaging findings of gastric body thickening are inconsistent with HCC disease recurrence. Secondary malignant neoplasm (eg, gastric cancer) occurs in about 3% of patients with HCC and is a consideration given radiographic findings, though the biopsy specimen showed no malignant neoplasm.4

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Article Information

Corresponding Author: James J. Harding, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 E 66th St, New York, NY 10065 (hardinj1@mskcc.org).

Published Online: September 22, 2022. doi:10.1001/jamaoncol.2022.3888

Conflict of Interest Disclosures: Dr Faleck reported personal fees from AzurRx, Equillium, and Mallinckrodt and support from National Cancer Institute P30-CA008748 outside the submitted work. Dr Harding reported personal fees from Adaptimmune, Bristol Myers Squibb, CytomX, Eli Lilly, Exelixis, Hepion, MedVir, Tempus, QED, Zymeworks; grants from Bristol Myers Squibb, Boehringer Ingelheim, Calithera, CytomX, Eli Lilly, Genoscience, Loxo, Novartis, Pfizer, Polaris, Yiviva, and Zymeworks; and support from Byron Wein and Anita Volz Liver Cancer Research Fund and National Cancer Institute P30-CA008748 outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information. We also thank Kinh Gian Do, MD, PhD, and Jinru Shia, MD, Memorial Sloan Kettering Cancer Center, for helpful discussions on the interpretation of radiographs and pathology slides. They did not receive compensation for these contributions.

References
1.
Yau  T , Park  JW , Finn  RS ,  et al.  Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459).   Lancet Oncol. 2022;23(1):77-90.PubMedGoogle ScholarCrossref
2.
Finn  RS , Qin  S , Ikeda  M ,  et al; IMbrave150 Investigators.  Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.   N Engl J Med. 2020;382(20):1894-1905.PubMedGoogle ScholarCrossref
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Cartwright  SL , Knudson  MP .  Evaluation of acute abdominal pain in adults.   Am Fam Physician. 2008;77(7):971-978.PubMedGoogle Scholar
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Shah  BK , Kandel  P , Khanal  A .  Second primary malignancies in hepatocellular cancer—a US population-based study.   Anticancer Res. 2016;36(7):3511-3514.PubMedGoogle Scholar
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Perini  RF , Camara  PR , Ferraz  JG .  Pathogenesis of portal hypertensive gastropathy.   Nat Clin Pract Gastroenterol Hepatol. 2009;6(3):150-158.PubMedGoogle ScholarCrossref
6.
Xing  P , Zhang  F , Wang  G ,  et al.  Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI.   J Immunother Cancer. 2019;7(1):341.PubMedGoogle ScholarCrossref
7.
Woodford  R , Briscoe  K , Tustin  R , Jain  A .  Immunotherapy-related gastritis.   Clin Med Insights Oncol. 2021;15:11795549211028570.PubMedGoogle Scholar
8.
Sugiyama  Y , Tanabe  H , Matsuya  T ,  et al.  Severe immune checkpoint inhibitor-associated gastritis.   Endosc Int Open. 2022;10(7):E982-E989.PubMedGoogle Scholar
9.
Tang  T , Abu-Sbeih  H , Luo  W ,  et al.  Upper gastrointestinal symptoms and associated endoscopic and histological features in patients receiving immune checkpoint inhibitors.   Scand J Gastroenterol. 2019;54(5):538-545.PubMedGoogle ScholarCrossref
10.
Santini  FC , Rizvi  H , Plodkowski  AJ ,  et al.  Safety and efficacy of re-treating with immunotherapy after immune-related adverse events in patients with NSCLC.   Cancer Immunol Res. 2018;6(9):1093-1099.PubMedGoogle ScholarCrossref
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