Recurrent bowel obstruction: unusual presentation of pembrolizumab-induced pancreatitis in annular pancreas

Rawson, Robert V.; Robbins, Elizabeth; Kapoor, Rony; Scolyer, Richard A.; Long, Georgina V.

doi:10.1016/j.ejca.2017.05.042

Cited by 12 publications

(6 citation statements)

References 21 publications

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“…Rawson et al described a 43-year-old man who had been treated with pembrolizumab for metastatic malignant melanoma and underwent pancreaticoduodenectomy due to recurrent bowel obstruction in the annular portion of the pancreas after pembrolizumab therapy. HE-stained sections from resected tissue samples showed acute on chronic pancreatitis with marked loss of pancreatic acinar cells, replacement fibrosis, mixed acute and chronic inflammatory cell infiltrates in the interstitial tissue, and no increase in the number of IgG4-positive cells ( 7 ). They also reported typical histological findings of neutrophil aggregation in many pancreatic ducts.…”

Section: Discussionmentioning

confidence: 99%

“…However, while there have been many case reports of ICI-induced pancreatic injury, there are only a few reports describing pathological findings. The pathological findings of ICI-induced pancreatitis described thus far include neutrophil-based infiltration and T lymphocyte-based infiltration, but these findings are inconsistent and poorly understood ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil Infiltration and Acinar-ductal Metaplasia Are the Main Pathological Findings in Pembrolizumab-induced Pancreatitis

et al. 2022

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The histopathological findings of immune checkpoint inhibitor (ICI)-induced pancreatitis have rarely been reported. A 56-year-old man with squamous cell carcinoma of the lung with bone metastasis was being treated with pembrolizumab, an anti-programmed cell death protein-1 antibody. After 13 doses, he was referred to our department due to pancreatitis. Despite characteristic symptoms of acute pancreatitis, imaging findings were similar to those of autoimmune pancreatitis. However, a histological examination showed neutrophil-based inflammatory cell infiltration and acinar-ductal metaplasia. Immunostaining showed CD8positive T lymphocyte infiltration. This case revealed the characteristic histopathology of pembrolizumabinduced pancreatitis, which was previously poorly understood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neutrophil Infiltration and Acinar-ductal Metaplasia Are the Main Pathological Findings in Pembrolizumab-induced Pancreatitis

et al. 2022

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“…Although the frequency of ICI-induced pancreatitis is lower than that of other irAEs, with its clinical characteris-tics still unclear, several case reports have been published (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Table shows the clinical characteristics of the 10 cases of ICI-induced pancreatitis that have been reported.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab-induced Focal Pancreatitis Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration

et al. 2022

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A 69-year-old man with advanced non-small-cell lung cancer was treated with pembrolizumab for 4 months. Three months after pembrolizumab was discontinued, computed tomography showed enlargement of the pancreatic head, with hypoattenuating areas in the pancreatic head to body. On endoscopic ultrasonography, the entire pancreatic parenchyma was hypoechoic. Endoscopic retrograde cholangiopancreatography showed narrowing of the main pancreatic duct at the pancreatic head. Endoscopic ultrasound-guided fineneedle aspiration showed inflammatory cell infiltration in the stroma but no neoplastic lesions. CD8-positve T cells were dominant over CD4-positive T cells in the infiltrating lymphocytes, and the patient was diagnosed with pembrolizumab-induced pancreatitis.

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“…Rawson et al [75] report the unusual case of a pembrolizumab induced pancreatitis presenting as small bowel obstruction; the diagnosis was made after surgery and histopathological examination, which revealed significant damage to the pancreas. The authors point out that the risks associated with immunotherapy can be higher than realized, since some of them are asymptomatic and remain undetected [75].…”

Section: Discussionmentioning

confidence: 99%

“…We found various reports of PD-1/PD-L1 induced diabetes mellitus [68][69][70][71][72][73][74]. A peculiar presentation of pembrolizumab induced pancreatitis was described as a small bowel perforation [75]. Few cases of ICI induced exocrine pancreatic insufficiency pointed out that this diagnosis must be kept in mind in patients presenting with diarrhea, since not all cases are caused by colitis.…”

Section: Pancreatic Toxicitymentioning

confidence: 99%

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

Radulescu

Crişan

Grapa

et al. 2021

JGLD

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Background and Aims: While immune checkpoint inhibitors therapy (ICI) is exceedingly effective, these drugs are associated with various immune-related adverse effects. As gastrointestinal, hepatic or pancreatic toxicity becomes more common, various reports of rare adverse effects have emerged, leading to a significant clinical and prognostic impact. We aimed to provide a systematic review of mainly case-reports on rare events, to help physicians to make an accurate and fast diagnosis. Methods: We performed a systematic review of the literature, using established MeSH terms: “immune checkpoint inhibitors”, “gastrointestinal tract”, “gastrointestinal diseases”, “liver”, “pancreas”, “nivolumab”, “ipilimumab”, the subheadings “adverse effects”, “toxicity” and the supplementary concepts “pembrolizumab”, “tremelimumab”, “atezolizumab”, “avelumab”, “durvalumab”, with defined inclusion criteria. Results: From 419 manuscripts initially selected, 74 reports of rare adverse events were included in our review. Special cases of neutrophilic gastritis, hemorrhagic gastritis, or even perforations were described at upper digestive tract. Different types of colitis were found secondary to ICI such as pseudomembranous, granulomatous, collagenous and microscopic colitis or even inflammatory bowel disease. In terms of liver toxicity, we found rare reports of cholangitis, granulomatous hepatitis, lipodystrophy and hepatic sinusoidal obstruction syndrome. Pancreas toxicity was rarely reported as severe pancreatitis, exocrine failure and diabetes mellitus. Conclusion: Although a complete check-up of every organ at every routine visit may not be practical, focus on symptoms, targeted laboratory and imaging testing may reveal rare organ damage. Raising awareness of the uncommon toxicities related to the immunotherapy is essential, as some rare events can lead to fatal outcomes.

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Recurrent bowel obstruction: unusual presentation of pembrolizumab-induced pancreatitis in annular pancreas

Cited by 12 publications

References 21 publications

Neutrophil Infiltration and Acinar-ductal Metaplasia Are the Main Pathological Findings in Pembrolizumab-induced Pancreatitis

Neutrophil Infiltration and Acinar-ductal Metaplasia Are the Main Pathological Findings in Pembrolizumab-induced Pancreatitis

Pembrolizumab-induced Focal Pancreatitis Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

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