scholarly journals Diagnosis and Management of Rectal Neuroendocrine Tumors (NETs)

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 771
Author(s):  
Francesco Maione ◽  
Alessia Chini ◽  
Marco Milone ◽  
Nicola Gennarelli ◽  
Michele Manigrasso ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Neuroendocrine Tumors ◽  
Lymphovascular Invasion ◽  
Muscularis Propria ◽  
Biological Behavior ◽  
Detection Rates ◽  
The Past ◽  
Intermediate Size ◽  
Well Differentiated ◽  
Metastatic Risk

Rectal neuroendocrine tumors (NETs) are rare, with an incidence of 0.17%, but they represent 12% to 27% of all NETs and 20% of gastrointestinal NETs. Although rectal NETs are uncommon tumors, their incidence has increased over the past few years, and this is probably due to the improvement in detection rates made by advanced endoscopic procedures. The biological behavior of rectal NETs may be different: factors predicting the risk of metastases have been identified, such as size and grade of differentiation. The tendency for metastatic diffusion generally depends on the tumor size, muscular and lymphovascular infiltration, and histopathological differentiation. According to the current European Neuroendocrine Tumor Society (ENETS) guidelines, tumors that are smaller than 10 mm and well differentiated are thought to have a low risk of lymphovascular invasion, and they should be completely removed endoscopically. Rectal NETs larger than 20 mm have a higher risk of involvement of muscularis propria and high metastatic risk and are candidates for surgical resection. There is controversy over rectal NETs of intermediate size, 10–19 mm, where the metastatic risk is considered to be 10–15%: assessment of tumors endoscopically and by endoanal ultrasound should guide treatment in these cases towards endoscopic, transanal, or surgical resection.

Small Neuroendocrine Tumors of the Whole Gastrointestinal Tract Performed Endoscopic or Surgical Resections Also Show Positive for Lymphovascular Invasion

Digestion ◽  
2021 ◽  
pp. 1-8
Author(s):  
Haruna Miyashita ◽  
Takuji Yamasaki ◽  
Yoshihiro Akita ◽  
Yoshitaka Ando ◽  
Yuki Maruyama ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Neuroendocrine Tumors ◽  
Tumor Size ◽  
Lymphovascular Invasion ◽  
Distant Metastases ◽  
High Rate ◽  
Ki 67 ◽  
Primary Endpoints ◽  
Invasion Impact ◽  
Prognostic Stratification

<b><i>Background and Aims:</i></b> In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. <b><i>Methods:</i></b> We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. <b><i>Results:</i></b> Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases &#x3c;5 mm, with a lymphovascular invasion rate of 8.7% for those 5–10 mm. Lymphovascular invasion ≤10% required a tumor size ≤8 mm, and lymphovascular invasion ≤5% required a tumor size ≤6 mm. A cutoff of 6 mm was identified, which yielded a sensitivity of 79% and a specificity of 63%. Even small GI-NETs grade 1 of the whole GI tract also showed positive for lymphovascular invasion. <b><i>Conclusions:</i></b> GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

scholarly journals Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors

Oncogenesis ◽  
2021 ◽  
Vol 10 (12) ◽  
Author(s):  
Angela M. Carter ◽  
Nilesh Kumar ◽  
Brendon Herring ◽  
Chunfeng Tan ◽  
Rachael Guenter ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Islet Cells ◽  
Tumor Development ◽  
Heterogeneous Population ◽  
Targeted Therapeutics ◽  
Pancreatic Neuroendocrine Tumors ◽  
The Past ◽  
Regulated Expression ◽  
Well Differentiated ◽  
Conditional Mouse Model

AbstractPancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in β-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Neuroendocrine Tumors of Meckel's Diverticula: Rare but Fare Well

2019 ◽  
Vol 85 (10) ◽  
pp. 1125-1128 ◽  
Author(s):  
James P. De Andrade ◽  
Andrew M. Blakely ◽  
Andrew H. Nguyen ◽  
Philip H. G. Ituarte ◽  
Susanne G. Warner ◽  
...  
Keyword(s):  
Lymph Node ◽  
Neuroendocrine Tumors ◽  
Lymphovascular Invasion ◽  
Metastatic Lymph Node ◽  
National Cancer Database ◽  
Tumor Characteristics ◽  
Node Disease ◽  
Node Metastases ◽  
Well Differentiated ◽  
Common Malignancy

Neuroendocrine tumors (NETs) are the most common malignancy arising in Meckel's diverticula (MDs). To date, there are no large series characterizing these tumors. The National Cancer Database was queried for patients with MD NETs (n = 162) from 2004 to 2014. Patient and tumor characteristics as well as outcomes were analyzed. MD NETs were more common in men (72.8%) at a median age of 62 years; 95.1 per cent of patients were white. All patients underwent surgery. Clinical M0 disease was present in 97.4 per cent of patients, and 88.2 per cent of tumors were well differentiated. Lymphovascular invasion was present in 13.2 per cent. Most (60.4%) tumors were less than 10 mm. Lymphadenectomy was performed in 32.9 per cent of patients, with 52.1 per cent of these found to have metastatic lymph node disease. Although most MD NETs are well differentiated, smaller than 10 mm, and do not have lymphovascular invasion, lymph node metastases are commonly found, suggesting that mesenteric lymphadenectomy with adequate resection of the small bowel may be necessary for adequate staging and disease clearance.

scholarly journals Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors

2021 ◽  
Author(s):  
Angela M Carter ◽  
Nilesh Kumar ◽  
Brendon Herring ◽  
Chunfeng Tan ◽  
Racheal Guenter ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Islet Cells ◽  
Tumor Development ◽  
Heterogeneous Population ◽  
Targeted Therapeutics ◽  
Pancreatic Neuroendocrine Tumors ◽  
The Past ◽  
Regulated Expression ◽  
Well Differentiated ◽  
Conditional Mouse Model

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bitransgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in beta-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. The utility of this model is enhanced by ability to form tumor-derived allografts. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Neuroendocrine Tumors of the Rectum: A 10-Year Review of Management

2011 ◽  
Vol 77 (2) ◽  
pp. 198-200 ◽  
Author(s):  
Jason R. Moore ◽  
Brian Greenwell ◽  
Kaylee Nuckolls ◽  
David Schammel ◽  
Nicholas Schisler ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Local Excision ◽  
Neuroendocrine Carcinoma ◽  
Residual Disease ◽  
Muscularis Propria ◽  
Positive Margins ◽  
Pathologic Evaluation ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Well Differentiated

Neuroendocrine tumors of the rectum constitute ∼19 per cent of gastrointestinal neuroendocrine tumors (NETs). The histologic characteristics of the tumor seem to be an indicative prognostic factor. Optimal treatment of NETS of the rectum has been widely debated, but more recent studies suggest that treatment depends upon the size. The medical records of 37 patients with NETS of the rectum were retrospectively reviewed. We reviewed their presentation, surgical treatment, pathology, and outcome. All pathological specimens were reviewed. Neuroendocrine tumors of the rectum were classified as either well-differentiated tumors, well-differentiated neuroendocrine carcinoma, or poorly differentiated neuroendocrine carcinoma. Evaluating tumor size, we found 35/37 patients had tumors less than 1 cm, 1 patient had a tumor between 1 and 2 cm, and one had a tumor greater than 2 cm. Pathologic evaluation of the tumors revealed that 35 of the tumors invaded the submucosa only, one invaded the muscularis propria, and one invaded the perirectal adipose tissue. The histopathologic features of the tumors revealed that 34 of the tumors were well-differentiated NETS with benign features, one tumor had invaded the submucosa, with angioinvasion, and two tumors were neuroendocrine carcinoma. Thirty-five patients underwent local excision. Eleven had reexcisions for positive margins. Two patients had local excision for recurrence, and one patient underwent low anterior resection (4 cm). Twelve patients had negative margins, 25 had positive margins. Eleven patients underwent reexcision. Six had no evidence of residual disease, and five had persistent positive margins and were offered no further treatment. Nineteen patients had positive margins and did not have reexcision. They all had tumors < 1 cm. Despite half of the lesions being resected with final pathologic positive margins, we have seen no significant influence on recurrence or overall survival. This raises the question of margin clearance in early lesions.

Beyond Promoter: The Role of Macrophage in Invasion and Progression of Renal Cell Carcinoma

2020 ◽  
Vol 15 (7) ◽  
pp. 588-596
Author(s):  
Haibao Zhang ◽  
Guodong Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Formation ◽  
Biological Behavior ◽  
Tumor Stem Cell ◽  
The Past ◽  
The Common

Renal cell carcinoma (RCC) is one of the common urologic neoplasms, and its incidence has been increasing over the past several decades; however, its pathogenesis is still unknown up to now. Recent studies have found that in addition to tumor cells, other cells in the tumor microenvironment also affect the biological behavior of the tumor. Among them, macrophages exist in a large amount in tumor microenvironment, and they are generally considered to play a key role in promoting tumorigenesis. Therefore, we summarized the recent researches on macrophage in the invasiveness and progression of RCC in latest years, and we also introduced and discussed many studies about macrophage in RCC to promote angiogenesis by changing tumor microenvironment and inhibit immune response in order to activate tumor progression. Moreover, macrophage interactes with various cytokines to promote tumor proliferation, invasion and metastasis, and it also promotes tumor stem cell formation and induces drug resistance in the progression of RCC. The highlight of this review is to make a summary of the roles of macrophage in the invasion and progression of RCC; at the same time to raise some potential and possible targets for future RCC therapy.

scholarly journals Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philippe Thuillier ◽  
David Bourhis ◽  
Jean Philippe Metges ◽  
Romain Le Pennec ◽  
Karim Amrane ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Linear Relation ◽  
Whole Body ◽  
Pet Ct ◽  
Non Linear ◽  
Well Differentiated ◽  
Analog Systems ◽  
Pet System ◽  
Dynamic Acquisition ◽  
Linear Regressions

AbstractTo present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1–5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs.

scholarly journals The Value of Alkaline Phosphatase-to-Albumin Ratio in Detecting Synchronous Metastases and Predicting Postoperative Relapses among Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Wentao Zhou ◽  
Yuan Fang ◽  
Xu Han ◽  
Tiantao Kuang ◽  
Xuefeng Xu ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Distant Metastasis ◽  
Vascular Invasion ◽  
Biological Behavior ◽  
Neuroendocrine Neoplasm ◽  
Albumin Ratio ◽  
Pancreatic Neuroendocrine Neoplasm ◽  
Synchronous Metastases ◽  
Well Differentiated ◽  
Synchronous Distant Metastasis

Backgrounds. Pancreatic neuroendocrine neoplasm (pNEN) is a highly heterogeneous entity, presenting widely varied biological behavior as well as long-term prognosis. Reliable biomarkers are urgently needed to make risk stratifications for pNEN patients, which could be beneficial to the development of individualized therapeutic strategy in the clinical practice. Here, we aimed to evaluate the predictive and prognostic roles of serum alkaline phosphatase-to-albumin ratio (APAR) in well-differentiated pNEN patients. Methods. We retrospectively analyzed the pathologically confirmed grade 1/2 pNEN patients, who were originally treated in our hospital from February 2008 to April 2018. Univariate and multivariate analyses were performed to assess the value of APAR in detecting synchronous metastases and predicting relapses following curative resections. Results. A total of 170 eligible cases were included into analysis. Logistic univariate analysis indicated APAR (P=0.002) was significantly associated with synchronous distant metastasis among well-differentiated pNEN patients, which was further demonstrated to be an independent risk factor by multivariate analysis (odds ratio 8.127, 95% confidence interval (CI) 2.105–31.372, P=0.002). For the prognostic value, APAR (P=0.007) was statistically associated with recurrence-free survival (RFS) in nonmetastatic resected pNEN patients, but it was not an independent predictor. Further subgroup analysis showed that APAR was independently related to RFS in patients with no nerve (hazard ratio (HR) 7.685, 95% CI 1.433–41.209, P=0.017) or vascular invasion (HR 4.789, 95% CI 1.241–18.473, P=0.023), respectively. Conclusion. APAR may work as a convenient pretreatment marker to detect synchronous distant metastasis for well-differentiated pNEN patients and predict recurrences for curatively resected cases without nerve or vascular invasion. However, these findings should be further verified in prospectively well-designed studies.

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