Primary Site Predicts Grade for Gastroenteropancreatic Neuroendocrine Tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and abstruse neoplasms with increasing incidence and clinical relevance. The National Cancer Data Base was examined to identify GEP-NETcases from 2004 to 2013. In total, 39,454 patients diagnosed with GEP-NET were identified. Median age was 61 years. Majority was female (50.13%), white (79.49%), and had low-grade neoplasms (84.39%). On univariate analysis, age, sex, race, primary site, tumor size, and regional lymph node involvement were associated with tumor grade (P < 0.0001). On multivariate analysis, older age [odds ratio (OR) = 9.57], gender (male, OR = 1.29), and race continued to be associated with high-grade neoplasms. The primary site also remained a significant predictor of tumor grade. High-grade neoplasms were more likely to arise from the esophagus (OR = 317.75), hepatobiliary system (OR = 23.15), colorectum (OR = 14.37), ampulla of Vater (OR = 11.61), and stomach (OR = 7.84) compared with the appendix (OR = 5.41), pancreas (OR = 5.31), and small bowel (referent). The tumor grade for GEP-NETs is highly dependent on the primary site, suggesting different sites may be biologically distinct diseases. A personalized approach to GEP-NET treatment, tailored to the site of origin, is imperative.

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Soluble cytotoxic T-lymphocyte–associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma

BMC Immunology ◽

10.1186/s12865-021-00422-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jiajia Liu ◽

Xiaoyi Tian ◽

Yan Wang ◽

Xixiong Kang ◽

Wenqi Song

Keyword(s):

T Lymphocyte ◽

Roc Curve ◽

Cytotoxic T Lymphocyte ◽

Tumor Grade ◽

Curve Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Low Grade ◽

High Grade ◽

Healthy Individuals ◽

Roc Curve Analysis

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.

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Cardio-Metabolic Indices and Metabolic Syndrome as Predictors of Clinical Severity of Gastroenteropancreatic Neuroendocrine Tumors

Frontiers in Endocrinology ◽

10.3389/fendo.2021.649496 ◽

2021 ◽

Vol 12 ◽

Author(s):

Luigi Barrea ◽

Giovanna Muscogiuri ◽

Roberta Modica ◽

Barbara Altieri ◽

Gabriella Pugliese ◽

...

Keyword(s):

Metabolic Syndrome ◽

Fatty Liver ◽

Neuroendocrine Tumors ◽

Progressive Disease ◽

Visceral Adiposity ◽

Clinical Severity ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Alcoholic Fatty Liver ◽

Cancer Data ◽

Early Predictors

BackgroundObesity, mainly visceral obesity, and metabolic syndrome (MetS) are major risk factors for the development of type 2 diabetes, cardiovascular diseases, and cancer. Data analyzing the association of obesity and MetS with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are lacking. Fatty liver index (FLI) is a non-invasive tool for identifying individuals with non-alcoholic fatty liver disease (NAFLD). Visceral adiposity index (VAI) has been suggested as a gender-specific indicator of adipose dysfunction. Both indexes have been proposed as early predictors of MetS. This study aimed to investigate the association of FLI VAI as early predictors of MetS with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).MethodsA cross-sectional, case–control, observational study was carried out at the ENETS Centers of Excellence Multidisciplinary Group for Neuroendocrine Tumors, University “Federico II”. VAI and FLI were calculated.ResultsWe enrolled 109 patients with histologically confirmed G1/G2 GEP-NET (53 M; 57.06 ± 15.96 years), as well as 109 healthy subjects, age, sex- and body mass index-matched. Forty-four GEP-NET patients were G2, of which 21 were with progressive disease, and 27 patients had metastases. GEP-NET patients had a higher value of VAI (p < 0.001) and FLI (p = 0.049) and higher MetS presence (p < 0.001) compared with controls. VAI and FLI values and MetS presence were higher in G2 than in G1 patients (p < 0.001), in patients with progressive disease, and in metastatic vs non-metastatic patients (p < 0.001). In addition, higher values of VAI and FLI and higher MetS presence were significantly correlated with the worst clinical severity of NENs. The cut-off values for the FLI and MetS to predict high grading of GEP-NETs and the presence of metastasis were also provided.ConclusionsThis is the first study investigating an association between VAI and FLI as early predictors of MetS and GEP-NET. Our findings report that the worsening of clinicopathological characteristics in GEP-NET is associated with higher presence of MetS, NAFLD, evaluated by FLI, and visceral adiposity dysfunction, evaluated by VAI. Addressing the clinical evaluation of MetS presence, NAFLD, and visceral adiposity dysfunction might be of crucial relevance to establish targeted preventive and treatment interventions of NEN-related metabolic comorbidities.

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Emerging Therapeutic Concepts and Latest Diagnostic Advancements Regarding Neuroendocrine Tumors of the Gynecologic Tract

Medicina ◽

10.3390/medicina57121338 ◽

2021 ◽

Vol 57 (12) ◽

pp. 1338

Author(s):

Tiberiu-Augustin Georgescu ◽

Roxana Elena Bohiltea ◽

Octavian Munteanu ◽

Florentina Furtunescu ◽

Antonia-Carmen Lisievici ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Neuroendocrine Carcinoma ◽

Classification System ◽

Who Classification ◽

Small Cell ◽

International Agency ◽

Low Grade ◽

High Grade ◽

Small Cell Neuroendocrine Carcinoma ◽

Female Genital

Neuroendocrine neoplasms (NENs) are particularly rare in all sites of the gynecological tract and include a variety of neoplasms with variable prognosis, dependent on histologic subtype and site of origin. Following the expert consensus proposal of the International Agency for Research on Cancer (IARC), the approach in the latest World Health Organization (WHO) Classification System of the Female Genital Tumours is to use the same terminology for NENs at all body sites. The main concept of this novel classification framework is to align it to all other body sites and make a clear distinction between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The previous WHO Classification System of the Female Genital Tumours featured more or less the same principle, but used the terms ‘low-grade neuroendocrine tumor’ and ‘high-grade neuroendocrine carcinoma’. Regardless of the terminology used, each of these two main categories include two distinct morphological subtypes: NETs are represented by typical and atypical carcinoid and NEC are represented by small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). High-grade NECs, especially small cell neuroendocrine carcinoma tends to be more frequent in the uterine cervix, followed by the endometrium, while low-grade NETs usually occur in the ovary. NENs of the vulva, vagina and fallopian tube are exceptionally rare, with scattered case reports in the scientific literature.

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Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan-cancer transcriptome analysis of a distinct entity

Cancer Cell International ◽

10.1186/s12935-019-1031-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 5

Author(s):

Dan Huang ◽

Fei Ren ◽

Shujuan Ni ◽

Cong Tan ◽

Weiwei Weng ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Expression Patterns ◽

Biological Behavior ◽

Low Grade ◽

High Grade ◽

Clinicopathologic Characteristics ◽

Signet Ring ◽

Cancer Transcriptome ◽

Male Patients ◽

Pan Cancer

Abstract Background and aim Amphicrine carcinoma, in which endocrine and epithelial cell constituents are present within the same cell, is very rare. This study characterized the clinicopathologic and survival analysis of this tumor, further compared the genetic diversities among amphicrine carcinoma and other tumors. Materials and methods The clinicopathologic characteristics and survival outcomes of amphicrine carcinoma in this study were analyzed. The pan-cancer transcriptome assay was utilized to compare the genetic expression profile of this entity with that of conventional adenocarcinoma or neuroendocrine tumors. Results Ten cases (all in male patients) were identified in the stomach or intestine, with a median patient age of 62 years. There were characteristic patterns in the tumors: tubular, fusion or single-file growth of goblet- or signet ring-like cells. Four tumors were classified as low-grade and 6 as high-grade according to the histologic architecture. All cases were positive for neuroendocrine markers (synaptophysin and chromogranin A) and showed intracellular mucin in the amphicrine components. Four cases exhibited mRNA expression patterns showing transcriptional homogeneity with conventional adenocarcinomas and genetic diversity from neuroendocrine tumors. During the follow-up period, 3 patients died of disease, all of whom had high-grade tumors. Patients with high-grade amphicrine carcinoma had worse outcomes than those with low-grade tumors. Conclusions This study confirms the morphological, immunostaining and transcriptome alterations in amphicrine carcinoma distinct from those in conventional adenocarcinomas and neuroendocrine tumors, but additional studies are warranted to determine the biological behavior and therapeutic response.

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Radiotherapy of Intracranial Astrocytomas

Neurosurgery ◽

10.1227/00006123-197909000-00001 ◽

1979 ◽

Vol 5 (3) ◽

pp. 301-308 ◽

Cited By ~ 97

Author(s):

Paul W. Scanlon ◽

William F. Taylor

Keyword(s):

Radiation Therapy ◽

Postoperative Radiotherapy ◽

Tumor Grade ◽

Low Grade ◽

Unexpected Finding ◽

High Grade ◽

Death Rates ◽

Brain Irradiation ◽

Total Brain ◽

Better Than

Abstract In a review of 417 intracranial astrocytomas treated radiotherapeutically at the Mayo Clinic from 1960 through 1969, the well-known correlation of tumor grade with survival was verified. Totally unexpected was the finding that age was fully as important a discriminant as tumor grade. Another unexpected finding was that patients treated with biopsy only followed by radiation therapy did as well as or slightly better than those subjected to resection followed by postoperative radiotherapy. We could not verify the importance to survival of either large dose or large volume radiotherapy, which has been emphasized by some. Patients receiving less than 1400 rets did just as well as or slightly better than those receiving more than 1400 rets. With low grade astrocytomas, survival beyond 4 years was significantly worse (higher death rates) in the group receiving more than 1400 rets. This suggested the possibility of radiation damage with delayed manifestations. We also could not verify an increased effectiveness for the generally accepted use of total brain irradiation for high grade gliomas.

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Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.514 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 514-514

Author(s):

Alberto Pimentel ◽

Abdel Karim Dip Borunda ◽

Luis Jonathan Bueno Rosario ◽

Gloria Martinez Martinez ◽

Miguel Angel Pluma ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Symptom Control ◽

Progression Free Survival ◽

Somatostatin Analogues ◽

Low Grade ◽

Common Symptom ◽

First Line ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Long Acting

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.

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The nonsurgical management of upper tract urothelial carcinoma: A role for active surveillance?

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.485 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 485-485

Author(s):

Jamil Syed ◽

Kevin Nguyen ◽

Juan Javier-Desloges ◽

Michael Leapman ◽

Jay D. Raman ◽

...

Keyword(s):

Alternative Therapy ◽

Tumor Grade ◽

Population Based ◽

Male Gender ◽

Low Grade ◽

High Grade ◽

Upper Tract ◽

Nonsurgical Management ◽

Co Morbidity ◽

Definitive Therapy

485 Background: Approximately 7% of patients with localized upper tract urothelial cancer (UTUC) are treated without definitive therapy. Understanding outcomes and alternative therapy would aid in counseling older patients with co-morbidities. Methods: We utilized the National Cancer Database to identify patients with localized UTUC managed non-surgically between 2004 and 2013. Patient demographics, co-morbidity, tumor grade, and chemotherapy and radiation utilization were recorded. Survival analyses were performed with the Kaplan-Meier method and a cox proportional hazard regression model. Results: We identified 3,157 (10.9%) patients with localized UTUC who did not receive definitive surgery. Median age was 79 years, 55% were males, 79% had government health insurance, and 68% had a CDS of 0. Tumor grade was low (grade 1 or 2) in 632 (36.4%) and high (grade 3 or 4) in 1104 (63.6%). Median overall survival (OS) for the cohort was 2.2 years, significantly shorter for patients with greater co-morbidities. Chemotherapy or radiation was performed in 294 (9.3%) and 197 (6.3%) patients respectively. There were no OS differences for individuals receiving chemotherapy. Of patients who received radiation therapy, the median OS was 1.4 vs 2.0 years, (p<0.001) favoring no radiation. Those with high grade tumors had worse survival (1.9 vs 3.8 years (p<0.001). Significant predictors of shorter OS included older age, male gender, higher CDS, and government insurance. Conclusions: In this population-based cohort, 10.9% of patients with localized UTUC were managed non-surgically. Radiation and chemotherapy were not routinely utilized, and did not demonstrate improved survival. Median OS was significantly shorter for those with higher grade disease, increasing co-morbidity profile, male gender, and those with government insurance status.

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Poor-grade aneurysmal subarachnoid hemorrhage: relationship of cerebral metabolism to outcome

Journal of Neurosurgery ◽

10.3171/jns.2004.100.3.0400 ◽

2004 ◽

Vol 100 (3) ◽

pp. 400-406 ◽

Cited By ~ 96

Author(s):

Asita Sarrafzadeh ◽

Daniel Haux ◽

Ingeborg Küchler ◽

Wolfgang R. Lanksch ◽

Andreas W. Unterberg

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Metabolism ◽

Univariate Analysis ◽

High Morbidity ◽

Low Grade ◽

High Grade ◽

Content Type ◽

Poor Grade ◽

Fisher Grade ◽

Fine Print

Object. The majority of patients with poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies (WFNS) Grades IV and V, have high morbidity and mortality rates. The objective of this study was to investigate cerebral metabolism in patients with low-compared with high-grade SAH by using bedside microdialysis and to evaluate whether microdialysis parameters are of prognostic value for outcome in SAH. Methods. A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 ± 12.9 years); these patients were studied for 162 ± 84 hours (mean ± standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I–III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed. In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03). Conclusions. Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future.

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Biochemical Signatures of Doppel Protein in Human Astrocytomas to Support Prediction in Tumor Malignancy

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/301067 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Paola Rognoni ◽

Laurent R. Chiarelli ◽

Sergio Comincini ◽

Alberto Azzalin ◽

Clelia Miracco ◽

...

Keyword(s):

Tumor Progression ◽

Tumor Grade ◽

Low Grade ◽

High Grade ◽

Molecular Processes ◽

Glial Tumor ◽

The Central Nervous System ◽

Membrane Bound ◽

Biochemical Features ◽

Testis Tissue

Doppel (Dpl) is a membrane-bound glycoprotein mainly expressed in the testis of adult healthy people. It is generally absent in the central nervous system, but its coding gene sequence is ectopically expressed in astrocytoma specimens and in derived cell lines. In this paper, we investigated the expression and the biochemical features of Dpl in a panel of 49 astrocytoma specimens of different WHO malignancy grades. As a result, Dpl was expressed in the majority of the investigated specimens (86%), also including low grade samples. Importantly, Dpl exhibited different cellular localizations and altered glycan moieties composition, depending on the tumor grade. Most low-grade astrocytomas (83%) showed a membrane-bound Dpl, like human healthy testis tissue, whereas the majority of high-grade astrocytomas (75%) displayed a cytosolic Dpl. Deglycosylation studies with N-glycosidase F and/or neuraminidase highlighted defective glycan moieties and an unexpected loss of sialic acid. To find associations between glial tumor progression and Dpl biochemical features, predictive bioinformatics approaches were produced. In particular, Decision tree and Nomogram analysis showed well-defined Dpl-based criteria that separately clustered low-and high-grade astrocytomas. Taken together, these findings show that in astrocytomas, Dpl undergoes different molecular processes that might constitute additional helpful tools to characterize the glial tumor progression.

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Classification and Treatment of Pediatric Gliomas in the Molecular Era

Children ◽

10.3390/children8090739 ◽

2021 ◽

Vol 8 (9) ◽

pp. 739

Author(s):

Peter Hauser

Keyword(s):

Wide Spectrum ◽

High Grade Glioma ◽

Tumor Grade ◽

Primary Treatment ◽

Low Grade ◽

High Grade ◽

Therapeutic Approaches ◽

Term Survival ◽

Low Grade Gliomas ◽

Leading Role

The overall survival of pediatric gliomas varies over a wide spectrum depending on the tumor grade. Low-grade gliomas have an excellent long-term survival, with a possible burden of surgery, irradiation, and chemotherapy; in contrast, high-grade gliomas generally have a short-term, devastating lethal outcome. Recent advances in understanding their molecular background will transform the classification and therapeutic approaches of pediatric gliomas. Molecularly targeted treatments may acquire a leading role in the primary treatment of low-grade gliomas and may provide alternative therapeutic strategies for high-grade glioma cases in the attempt to avoid the highly unsuccessful conventional therapeutic approaches. This review aims to overview this progress.

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