Background and Aims
Therapy and prognosis of pancreatic neuroendocrine tumors (PanNETs) are strictly related
to the Ki-67 index, which defines tumor grading. The criterion standard for the assessment
of grading of PanNETs is EUS-guided FNA (EUS-FBAFNA) or EUS-guided fine-needle biopsy
sampling (EUS-FNB). Because data on diagnostic accuracy of EUS-FNA and EUS-FNB are
heterogeneous, we aimed to analyze the variability in concordance between EUS grading
and surgical grading.
Methods
The MEDLINE, SCOPUS, and EMBASE databases were searched until November 2021 to identify
studies reporting the concordance rate between EUS grading and surgical grading. The
study was conducted in accordance with Preferred Reporting Items for Systematic Reviews
and Meta-Analyses guidelines. Pooled events were calculated using a random-effects
model and expressed in terms of pooled prevalence rates. A multivariate meta-regression
was performed to find possible sources of heterogeneity. Where available, individual
data were analyzed.
Results
Twenty-six studies with 864 patients undergone EUS-FNA or EUS-FNB and surgical resection
for PanNETs were included. The pooled estimate rate for the overall concordance of
EUS grading and surgical grading was 80.3% (95% confidence interval, 75.6-85.1). Undergrading
(EUS grading < surgical grading) was significantly more frequent with respect to overgrading
(14.7% vs 3.5%, P < .001). Individual data analysis showed that among nonconcordant patients, the median
Ki-67 difference was 3% (interquartile range, 2-6.15). The type of World Health Organization
classification adopted and the median lesion diameter were significantly associated
with heterogeneity at meta-regression.
Conclusions
EUS is an accurate technique in defining grading in patients with PanNETs, but a margin
of error still exists, which should be the focus of future studies to minimize the
risk of over- and/or undertreatment.
Abbreviations:
EUS-FNB (EUS-guided fine-needle biopsy sampling), PanNET (pancreatic neuroendocrine tumor), WHO (World Health Organization)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Gastrointestinal EndoscopyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Pancreatic neuroendocrine tumors: nosography, management and treatment.Int J Surg. 2016; 28: S156-S162
- Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States.JAMA Oncol. 2017; 3: 1335-1342
- Epidemiologic trends and prognostic risk factors of patients with pancreatic neuroendocrine neoplasms in the US: an updated population-based study.Future Oncol. 2021; 17: 549-563
- ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors.Neuroendocrinology. 2016; : 153-171
- Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors.Endocr Relat Cancer. 2008; 15: 409-427
- Clinical pathology of endocrine tumors of the pancreas. Analysis of autopsy cases.Dig Dis Sci. 1991; 36: 933-942
- Is the real prevalence of pancreatic neuroendocrine tumors underestimated? A retrospective study on a large series of pancreatic specimens.Neuroendocrinology. 2019; 109: 165-170
- Ki-67 predicts disease recurrence and poor prognosis in pancreatic neuroendocrine neoplasms.Surgery. 2012; 152: 107-113
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 29;372:n71.
- WHO classification of tumours of the digestive system.No. Ed. 4, Switzerland, World Health Organization2010
- WHO classification of tumours of endocrine organs. International Agency for Research on Cancer.(IARC), 2017 (Ed. 4, France)
- Statistical analysis of individual participant data meta-analyses: a comparison of methods and recommendations for practice.PLoS One. 2012; 7: e46042
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177e88
- Quantifying heterogeneity in a meta-analysis.Stat Med. 2002; 21: 1539-1558
- Bias in meta-analysis detected by a simple, graphical test.Br Med J. 1997; 315: 629-634
- The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.2014 (Available from:) (Accessed October 20, 2022)
- Grading of pancreatic neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspiration using Ki-67 index and 2017 World Health Organization criteria: an analysis of 32 cases.Cytojournal. 2020; 17: 21
- Diagnostic accuracy of EUS-FNA in the evaluation of pancreatic neuroendocrine neoplasms grading: Possible clinical impact of misclassification.Endosc Ultrasound. 2021; 10: 372-380
- Pancreatic neuroendocrine neoplasm: correlation between computed tomography enhancement patterns and prognostic factors of surgical and endoscopic ultrasound-guided fine-needle aspiration biopsy specimens.Abdom Imag. 2013; 38: 358-366
- The usefulness of endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic neuroendocrine tumors based on the World Health Organization classification.Scand J Gastroenterol. 2014; 49: 1367-1374
- Efficacy of endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors.Scand J Gastroenterol. 2016; 51: 245-252
- Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading.World J Gastroenterol. 2015; 21: 8118-8124
- Histological diagnosis and grading of pancreatic neuroendocrine tumor by endoscopic ultrasound-guided fine needle biopsy using a 25-gauge needle with a core trap: a multicenter prospective trial.Pancreatology. 2020; 20: 1428-1433
- Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors.Endoscopy. 2014; 46: 32-38
- Ki-67 grading of nonfunctioning pancreatic neuroendocrine tumors on histologic samples obtained by EUS-guided fine-needle tissue acquisition: a prospective study.Gastrointest Endosc. 2012; 76: 570-577
- Pancreatic neuroendocrine tumors: accurate grading with Ki-67 index on fine-needle aspiration specimens using the WHO 2010/ENETS criteria.Cancer Cytopathol. 2014; 122: 770-778
- Reliability of Ki-67 determination in FNA samples for grading pancreatic neuroendocrine tumors.Endocrine Pathol. 2016; 27: 276-283
- The diagnostic value of FNA biopsy in grading pancreatic neuroendocrine tumors.Cancer Cytopathol. 2018; 126: 170-178
- Endoscopic ultrasound-guided fine-needle biopsy is superior to fine-needle aspiration in assessing pancreatic neuroendocrine tumors.Endosc Int Open. 2019; 07: E1281-E1287
- Ki-67 proliferation index in neuroendocrine tumors: Can augmented reality microscopy with image analysis improve scoring?.Cancer Cytopathol. 2020; 128: 535-544
- Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors.Pancreatology. 2021; 21: 443-450
- Accuracy of grading pancreatic neuroendocrine neoplasms with Ki-67 index in fine-needle aspiration cellblock material.Cytopathology. 2019; 30: 187-193
- Pancreatic neuroendocrine tumours: the role of endoscopic ultrasound biopsy in diagnosis and grading based on the WHO 2017 classification.Dig Dis. 2019; 37: 325-333
- Grading by the Ki-67 labeling index of endoscopic ultrasound-guided fine needle aspiration biopsy specimens of pancreatic neuroendocrine tumors can be underestimated.Pancreas. 2018; 47: 1296-1303
- Diagnostic accuracy and clinical significance of the fine needle aspiration Ki-67 labelling index in pancreatic endocrine tumours.Endocr Relat Cancer. 2011; 18: L1-L3
- Ki-67 cytological index can distinguish well-differentiated from poorly differentiated pancreatic neuroendocrine tumors: a comparative cytohistological study of 53 cases.Virch Arch. 2014; 465: 49-55
- Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine needle aspiration: high reproducibility and inter-observer agreement of the Ki-67 labelling index.Cytopathology. 2014; 25: 389-395
- Accuracy of pancreatic neuroendocrine tumour grading by endoscopic ultrasound-guided fine needle aspiration: analysis of a large cohort and perspectives for improvement.Neuroendocrinology. 2018; 106: 158-166
- Fine-needle aspiration-based grading of pancreatic neuroendocrine neoplasms using Ki-67: Is accurate WHO grading possible on cytologic material?.J Am Soc Cytopathol. 2018; 7: 154-159
- Grading pancreatic neuroendocrine tumors by Ki-67 index evaluated on fine-needle aspiration cell block material.Am J Clin Pathol. 2020; 153: 74-81
- The role of endoscopic ultrasound-guided Ki67 in the management of non-functioning pancreatic neuroendocrine tumors.Clin Endosc. 2020; 53: 213-220
- Ki-67 and presence of liver metastases identify different progression-risk classes in pancreatic neuroendocrine neoplasms (pNEN) undergoing resection.Eur J Surg Oncol. 2019; 45: 755-760
- EUS-guided radiofrequency ablation as an alternative to surgery for pancreatic neuroendocrine neoplasms: Who should we treat?.Endosc Ultrasound. 2019; 8: 220-226
- Fork-tip needle biopsy versus fine-needle aspiration in endoscopic ultrasound-guided sampling of solid pancreatic masses: a randomized crossover study.Endoscopy. 2020; 52: 454-461
- Randomized trial comparing fork-tip and side-fenestrated needles for EUS-guided fine-needle biopsy of solid pancreatic lesions.Gastrointest Endosc. 2020; 92: 648-658
- Improving the yield of EUS-guided histology.Endosc Ultrasound. 2018; 7: 301
- Heterogeneity of tumor prognostic markers: a reproducibility study applied to liver metastases of pancreatic endocrine tumors.Mod Pathol. 2008; 22: 273-281
- Use of quantitative endoscopic ultrasound elastography for diagnosis of pancreatic neuroendocrine tumors.Endosc Ultrasound. 2016; 5: 342
- Contrast-enhanced harmonic endoscopic ultrasound-guided fine-needle aspiration versus standard fine-needle aspiration in pancreatic masses a meta-analysis.Expert Rev Gastroenterol Hepatol. 2021; 15: 821-828
- Dual-tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT scan and G1-G2 non-functioning pancreatic neuroendocrine tumors: a single-center retrospective evaluation of 124 non-metastatic resected cases.Neuroendocrinology. 2022; 112: 143-152
- Endoscopic ultrasound features associated with malignancy and aggressiveness of nonhypovascular solid pancreatic lesions: results from a prospective observational study.Ultrasch Med. 2021; 42: 167-177
- Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: limitations to apply guidelines into real life.Surgery. 2019; 166: 157-163
Article Info
Publication History
Published online: July 18, 2022
Accepted:
July 8,
2022
Received:
February 7,
2022
Footnotes
DISCLOSURE: All authors disclosed no financial relationships.
DIVERSITY, EQUITY, AND INCLUSION: We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the language of the study questionnaires reflected inclusion.
Identification
Copyright
© 2022 by the American Society for Gastrointestinal Endoscopy
