Pathologic Grade and Tumor Size are Associated with Recurrence-Free Survival in Patients with Duodenal Neuroendocrine Tumors

Untch, Brian R.; Bonner, Keisha; Roggin, Kevin K.; Reidy‐Lagunes, Diane; Klimstra, David S.; Schattner, Mark; Fong, Yuman; Allen, Peter J.; D’Angelica, Michael I.; DeMatteo, Ronald P.; Jarnagin, William R.; Kingham, T. Peter; Tang, Laura H.

doi:10.1007/s11605-014-2456-x

Cited by 70 publications

(69 citation statements)

References 13 publications

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“…Corresponding results were also reported in the previous studies of D-NET [5,19,22]. In addition, only 4 cases had functional or hormonal syndrome (ZES with gastrin excessive), which is also similar to previous reports; 50-98% of D-NETs present no functional syndrome despite the positive immunoreactivity for gastrin, somatostatin, and/or serotonin in majority of D-NETs [5].…”

Section: Discussionsupporting

confidence: 89%

“…Kim et al [22 ]also reported that 33 patients with D-NETs measuring ≤10 mm in diameter and confined to the submucosa demonstrated no recurrence following ER providing the absence of metastasis revealed by CT at the time of procedure. However, other studies did report metastasis in such tumors [11,19]. In our present study, a tumor size of 11-20 mm turned out to be a significant risk factor for metastasis compared to that of ≤10 mm; 3 patients with tumors of ≤10 mm in diameter including a case harboring only a 2-mm tumor did develop metastasis.…”

Section: Discussioncontrasting

confidence: 50%

“…Third, all the included NAD-NETs in our present study were ≤20 mm in diameter. Most of the previous studies on D-NETs included those of >20 mm in diameter or ampullary D-NETs [8,10,11,12,14,16,17,18,19], the latter having a growth pattern different from that of NAD-NET [7,8,9,10]. For example, Burke et al [10] reported the pathological finding of 99 D-NETs but 42 of them were >20 mm in diameter and included ampullary tumors.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the treatment strategy of NAD-NETs of 10-20 mm is also not standardized [7,12,13,14] due to the rarity of NAD-NET compared to gastric NET or colorectal NET, which makes it difficult to conduct a larger study [15]. The great majority of previous studies on NAD-NETs were limited to single-institution studies with a small number of cases or including ampullary tumors [12,14,16,17,18,19]. However, D-NETs have recently been detected at much earlier stages and in smaller sizes [6], which make it clinically pivotal to identify the risk factors of metastasis in NAD-NETs ≤20 mm in diameter.…”

Section: Introductionmentioning

confidence: 99%

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The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter

et al. 2017

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Background/Aims: The treatment strategy for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) ≤20 mm in diameter has not been established. In this study, we aimed to evaluate the detailed characteristics of NAD-NETs ≤20 mm in diameter to clarify the risk factors of subsequent metastasis. Methods: The patients with NAD-NETs ≤20 mm in diameter who had been treated at 12 institutions between 1992 and 2013 were enrolled. Clinical records were retrieved, and histopathological findings of all cases were centrally reviewed by 2 pathologists. Results: We studied 49 patients with a mean follow-up period of 66.5 months. Thirty-five patients were initially treated with endoscopic resection (ER), and 14 with surgery. A univariate analysis revealed the ORs and 95% CIs of the risk factors for metastasis were lymphovascular invasion (12.5 [2.01-77.9]), multiple tumors (9.75 [1.46-65.4]), a tumor size of 11-20 mm (6.67 [1.21-36.6]), and World Health Organization grade G2 (7.13 [1.16-43.9]). Five-year overall and disease-specific survival rates were 86.1 and 97.2%, respectively. Conclusion: This is the first study to demonstrate the risk factors of metastasis in NAD-NETs ≤20 mm in diameter. These findings may be helpful for determining the appropriate therapeutic approach and the clinical strategy of treatment following ER.

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Section: Discussionsupporting

confidence: 89%

Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter

et al. 2017

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“…The manifold population of neuroendocrine neoplasms (NENs) arising in the duodenal mucosa and ampullary region has been investigated in several papers, leading to the characterization of various tumor entities according to histological structure, hormonal expression, clinical profile, genetic background and/or patient outcome [1,2,3,4,5,6,7]. Most were low-grade tumors, ranging from reportedly self-limiting gangliocytic paragangliomas (GPs) to a variety of well-differentiated epithelial neuroendocrine tumors (NETs).…”

Section: Introductionmentioning

confidence: 99%

Four Neuroendocrine Tumor Types and Neuroendocrine Carcinoma of the Duodenum: Analysis of 203 Cases

Rosa²,

et al. 2016

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Background: Several types of neuroendocrine neoplasms (NENs) have been described in the duodenal tract, from low-grade tumors (NETs) to high-grade neuroendocrine carcinomas (NECs). A comprehensive analysis of histology, hormonal profile and prognostic parameters of a sufficiently large duodenal NEN series to cover all main kinds of neoplasms is however lacking. Methods: We collected a retrospective series of 203 duodenal wall and ampullary region NENs, from six specialized endocrine pathology centers. All were characterized histopathologically and histochemically, and 190 were followed for a median of 9 years. Results: Twenty-seven poorly differentiated NECs, mostly from the ampullary region, were identified and shown to lead to patient demise in a median of 10 months. Among 176 NETs, four subtypes were characterized, including 20 gastrinomas, 37 ampullary-type somatostatin-producing NETs (ASTs), 12 gangliocytic paragangliomas (GPs) and 106 nonfunctioning NETs (nfNETs). ASTs and GPs were mostly localized in the ampullary/periampullary region, while gastrinomas and nfNETs were mainly from the proximal duodenum. ASTs and gastrinomas showed high rates of local infiltration (especially lymphoinvasion and deep duodenal wall/pancreatic tissue invasion) and lymph node metastasis, while nfNETs had significantly lower and more size-dependent local invasive potential. Disease-specific survival differed significantly between NETs and NECs, though not among NET subtypes. NET cases with distant metastases (n = 23) were significantly associated with larger size, higher proliferative grade, lymphovascular invasion, deep invasion and local lymph node metastasis. Conclusion: Our careful analysis of a large series of duodenal NENs identified five histologically and prognostically different histotypes of potential clinical relevance.

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Duodenal neuroendocrine tumors: Impact of tumor size and total number of lymph nodes examined

Zhang

Tsilimigras

et al. 2019

Journal of Surgical Oncology

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Background The current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET). Methods Patients who underwent curative resection for dNETs between 1997‐2016 were identified from 8 high‐volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cut‐off of TNLE relative to LNM was determined. Results Among 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51‐68) years and median tumor size was 1.2 cm (IQR, 0.7‐2.0 cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (≤1 cm:52.2% vs 1‐2 cm:61.4% vs >2 cm:93.8%; P < .05). Similarly, the incidence of LNM increased with dNET size (≤1 cm: 40.0% vs 1‐2 cm:65.7% vs >2 cm:80.0%; P < .05). TNLE ≥ 8 had the highest discriminatory power relative to the incidence of LNM (area under the curve = 0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR] = 0.9; 95% confidence intervals [95%CI], 0.4‐2.3), G2/G3 tumor grade was (HR = 1.5; 95%CI, 1.0‐2.1). Conclusions While the incidence of LNM directly correlated with tumor size, patients with dNETs ≤ 1 cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.

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Pathologic Grade and Tumor Size are Associated with Recurrence-Free Survival in Patients with Duodenal Neuroendocrine Tumors

Abstract: Tumor grade and size are associated with recurrence-free survival in duodenal neuroendocrine tumors. When feasible, a less aggressive surgical approach to treat low-grade and low-stage duodenal NETs should be considered.

Cited by 70 publications

References 13 publications

The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter

The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter

Four Neuroendocrine Tumor Types and Neuroendocrine Carcinoma of the Duodenum: Analysis of 203 Cases

Duodenal neuroendocrine tumors: Impact of tumor size and total number of lymph nodes examined

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