Basing Treatment Strategy for Non-functional Pancreatic Neuroendocrine Tumors on Tumor Size

Kishi, Yoji; Shimada, Kazuaki; Nara, Satoshi; Esaki, Minoru; Hiraoka, Nobuyoshi; Kosuge, Tomoo

doi:10.1245/s10434-014-3701-y

Cited by 73 publications

(53 citation statements)

References 30 publications

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“…Consequently, observation has even been suggested as the approach for patients having a tumour smaller than 1.5 cm. However, risk of distant metastases increases sharply with a larger PNEN size [48]. This is in agreement with the present study showing an association between tumour size, pM1 (p = 0.025), and invasion in the blood vessels (p = = 0.045), the precursor lesion of distant metastases.…”

Section: Tumour Sizesupporting

confidence: 93%

“…This is in agreement with the present study showing an association between tumour size, pM1 (p = 0.025), and invasion in the blood vessels (p = = 0.045), the precursor lesion of distant metastases. In addition, larger PNEN size has been found to correlate with LN metastases [48]. Considering the molecular basis of PNEN growth, the tumour size in the present study showed an association with Ki-67 (p = = 0.022) and a trend towards association with vimentin expression (p = 0.051).…”

Section: Tumour Sizesupporting

confidence: 59%

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Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Simtniece¹,

Vanags²,

Štrumfa³

et al. 2015

pjp

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The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p < 0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p = 0.022), the World Health Organization 2004 and 2010 classification grades (p = 0.021 and p = 0.002), stage (p = 0.028) and mitotic count (p = 0.007) but among molecular markers -with CK19 (p = 0.033) and vimentin (p = 0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p = 0.018), pR (p = 0.025), vascular (p = 0.020), perineural (p = 0.026) and lymphatic invasion (p = 0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.

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Section: Tumour Sizesupporting

confidence: 93%

Section: Tumour Sizesupporting

confidence: 59%

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Simtniece¹,

Vanags²,

Štrumfa³

et al. 2015

pjp

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“…Pancreas neuroendocrine tumors (P‐NETs) are the most common subgroup of GEP‐NETs. Several clinicopathologic variables including tumor size and margin status have been found to be predictors of survival . However, the prognostic importance of nodal metastasis has remained controversial in several recent population‐based studies .…”

Section: Introductionmentioning

confidence: 99%

Duodenal neuroendocrine tumors: Somewhere between the pancreas and small bowel?

Gamboa

Liu

Lee

et al. 2019

Journal of Surgical Oncology

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Background While sub‐2 cm pancreatic neuroendocrine tumors (NETs) are often observed, small bowel‐NETs undergo resection and lymphadenectomy regardless of size. Aim was to define the natural history of duodenal (D‐NETs), determine the role of resection, and define the factors associated with overall survival (OS) after resection. Methods National Cancer Database (2004‐2014) was queried for the patients with nonmetastatic/nonfunctional D‐NETs. Local resection (LR): local excision/polypectomy/excisional biopsy. Anatomic resection (AR): radical surgery. Tumor size was divided into less than 1 cm, 1 to 2 cm, and ≥2 cm. Propensity score weighting was used to create balanced resection and no‐resection cohorts. The primary endpoint was OS. Results Among 5502 patient, the median age was 65 years. The median follow‐up was 49 months. The median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954; LR: 61%, AR: 39%). Lymph node (LN) resection was performed in 26% (43% had metastasis). A total of 74% had negative margins. Resection and no‐resection cohorts were propensity score weighted for age/sex/race/Charlson‐Deyo score/tumor grade (all independently associated with OS on multivariable analysis). Resection was associated with improved median OS compared to no resection in all sizes (<1 cm: median not reached vs 194 months; 1‐2 cm: median not reached vs 56 months; >2 cm: median not reached vs 90 months; all P < .01). Subset analysis of each resection size cohort demonstrated that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all P > .05). Conclusion Patients with nonmetastatic and nonfunctional D‐NETS should be considered for resection regardless of tumor size. Given the lack of prognostic value, the resection type and extent of LN retrieval should be tailored to each patient's clinical picture and safety profile.

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“…However, aggressive tumors with early metastases and postsurgical recurrence have also been reported . Curative resection has been considered the first‐line treatment for most patients with locoregional PNETs, while surgery as a suitable option for some small tumors with low‐risk recurrence remains controversial …”

mentioning

confidence: 99%

“…2 Curative resection has been considered the first-line treatment for most patients with locoregional PNETs, while surgery as a suitable option for some small tumors with low-risk recurrence remains controversial. 3 Information on recurrence is helpful to inform patients about the probability of treatment success and prognosis following surgery. Particularly, accurate assessment of the risk of recurrence may not only assist with patient counseling and guide treatment but also help manage follow-up and reduce overtreatment in low-risk recurrence patients.…”

mentioning

confidence: 99%

MRI‐based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection

Sun

Zhang

et al. 2018

Magnetic Resonance Imaging

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Background Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow‐up, and avoid futile treatments. Purpose To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features. Study Type Retrospective. Population In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs. Field Strength/Sequences 1.5 T MR, including T1‐weighted, T2‐weighted, and diffusion‐weighted imaging sequences. Assessment Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists. Statistical Tests Uni‐ and multivariable analyses for recurrence‐free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI‐based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C‐index, calibration, and decision curve analyses. Results MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C‐index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C‐index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature. Data Conclusion MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies. Level of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397–409.

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Basing Treatment Strategy for Non-functional Pancreatic Neuroendocrine Tumors on Tumor Size

Abstract: Because PNETs ≤15 mm in size have little risk of metastases or recurrence, careful observation with serial image studies is acceptable. Once the tumor size exceeds 15 mm, the risk of metastases and recurrence increases significantly.

Cited by 73 publications

References 30 publications

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

Duodenal neuroendocrine tumors: Somewhere between the pancreas and small bowel?

MRI‐based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection

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