Woo Hyun Paik1, Hee Seung Lee2, Kyong Joo Lee3, Sung Ill Jang4, Woo Jin Lee5, Jin-Hyeok Hwang6, Chang Min Cho7, Chang-Hwan Park8, Jimin Han9, Sang Myung Woo5, Seok Jeong10, Hyung Ku Chon11, Tae Nyeun Kim12, Jun Kyu Lee13, Joung-Ho Han14, Jai Hoon Yoon15, Yong-Tae Kim16, Jae Hee Cho17. 1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea. 2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. 3. Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju, South Korea. 4. Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. 5. Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea. 6. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. 7. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea. 8. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea. 9. Division of Gastroenterology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, South Korea. 10. Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea. 11. Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, South Korea. 12. Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea. 13. Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, South Korea. 14. Department of Internal Medicine, Chungbuk National University College of Medicine, Chungbuk National University Hospital, Cheongju, South Korea. 15. Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Seoul Hospital, Seoul, South Korea. 16. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea. Electronic address: yongtkim@snu.ac.kr. 17. Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: jhcho9328@yuhs.ac.
Abstract
BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.
BACKGROUND:Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.