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Evaluation of Local Recurrence of Pancreatic Cancer by KRAS Mutation Analysis Using Washes from Endoscopic Ultrasound-Guided Fine-Needle Aspiration

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Abstract

Background and Aims

The sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing the recurrence of pancreatic cancer is usually low because of difficulties in obtaining adequate samples for pathological examinations. We evaluated the efficacy of highly sensitive KRAS mutation analysis using EUS-FNA washes to detect cancer recurrence.

Methods

Nineteen consecutive patients with suspected pancreatic cancer recurrence after surgical resection were enrolled. All underwent EUS-FNA, and samples were obtained for pathological examination. After the first session, the inside of the FNA needle was washed with saline for DNA extraction. KRAS mutations were examined using digital droplet PCR (dPCR).

Results

The median needle puncture number used to obtain adequate pathological samples was two (range 1–6). In ten patients pathologically diagnosed with malignant pancreatic cancer, nine patients tested positive for a KRAS mutation. All patients who were not diagnosed with a malignant pancreatic cancer tested negative for a KRAS mutation. About half of surgically resected primary cancers (9/19) showed double KRAS mutations (G12V and G12D); however, all but one wash sample showed a single KRAS mutation, G12D. After including one patient who showed a malignant recurrence during follow-up, the sensitivities of a pathological diagnosis and KRAS analysis to detect recurrence were 90.9% and 81.8%, respectively.

Conclusions

KRAS mutation analysis of needle wash samples using dPCR is a new methodology for the diagnosis of the local recurrence of pancreatic cancer. The diagnostic ability of dPCR with a one-time needle wash sample was comparable to a pathological diagnosis with multiple samplings.

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Abbreviations

EUS-FNA:

Endoscopic ultrasound-guided fine-needle aspiration

dPCR:

Digital droplet PCR

PD:

Pancreaticoduodenectomy

SSPPD:

Subtotal stomach-preserving pancreaticoduodenectomy

DP:

Distal pancreatectomy

TP:

Total pancreatectomy

DP-CAR:

Distal pancreatectomy with an en bloc celiac axis resection

CA:

Celiac artery

SMA:

Superior mesenteric artery

CHA:

Common hepatic artery

FFPE:

Formalin-fixed paraffin-embedded

ROSE:

Rapid on-site evaluation

UICC:

International Union against Cancer

TNM:

Tumor–node–metastasis

IQR:

Interquartile range

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Kazuyuki Matsumoto, Hironari Kato, Kazuhiro Nouso, Soichiro Ako, Hideaki Kinugasa, Shigeru Horiguchi, Yosuke Saragai, Saimon Takada, Shuntaro Yabe, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda & Hiroyuki Okada

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  1. Kazuyuki Matsumoto
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  2. Hironari Kato
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  3. Kazuhiro Nouso
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  4. Soichiro Ako
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  5. Hideaki Kinugasa
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  6. Shigeru Horiguchi
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  7. Yosuke Saragai
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  13. Hiroyuki Okada
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Contributions

KM, HK, and KN were involved in conception and design of the research and wrote the paper. SA and HK analyzed and interpreted the data. YS, ST, SY, SM, DU, and TT were involved in critical revision of the article for important intellectual content. HO was involved in final approval of the article. All authors read and approved the final manuscript.

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Correspondence to Kazuhiro Nouso.

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Matsumoto, K., Kato, H., Nouso, K. et al. Evaluation of Local Recurrence of Pancreatic Cancer by KRAS Mutation Analysis Using Washes from Endoscopic Ultrasound-Guided Fine-Needle Aspiration. Dig Dis Sci 65, 2907–2913 (2020). https://doi.org/10.1007/s10620-019-06006-6

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  • DOI: https://doi.org/10.1007/s10620-019-06006-6

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