Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

Jiang, Mengjie; Tan, Yinuo; Li, Xiaofen; Fu, Jianfei; Hu, Hanguang; Ye, Xianyun; Cao, Ying; Xu, Jinghong; Yuan, Ying

doi:10.1155/2017/4206172

Cited by 11 publications

(8 citation statements)

References 34 publications

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“…26 The results of the two studies on survival differences between colonic NECs and MiNENs are also different. 10,11 In addition, two studies on appendiceal MiNEN found that MiNEN is a more aggressive clinical entity than both goblet cell carcinoid of the appendix and carcinoid tumors of the appendix. 21,27 La Rosa et al and Klöppel et al 6,28 considered that some clinical differences between NECs and MiNENs might be site-related.…”

Section: Discussionmentioning

confidence: 99%

“…As for the colon, the results are also varied. 10 , 11 In addition, NENs are recognized as a heterogeneous family with multiple biological and clinical behaviors. 12 – 14 Therefore, it is unclear whether the inconsistent prognostic results between NECs and MiNENs are due to the high heterogeneity of NENs or site-related clinical differences.…”

Section: Introductionmentioning

confidence: 99%

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Do neuroendocrine carcinomas and mixed neuroendocrine–non-neuroendocrine neoplasm of the gastrointestinal tract have the same prognosis? A SEER database analysis of 12,878 cases

Shi

Meng

et al. 2020

Therapeutic Advances in Endocrinology

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Background: Neuroendocrine carcinomas (NECs) and mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) in the gastrointestinal (GI) tract are both rare and malignant; however, it is unclear whether their prognosis is the same. Methods: In this cross-sectional study, a total of 12,878 patients with NEC or MiNEN in the GI tract were reviewed retrospectively by searching the Surveillance, Epidemiology, and End Results ( SEER) program database. Next, we compared the characteristics and survival between patients with NEC or MiNEN and further analyzed the prognostic factors for the patients. Results: The data showed that patients with MiNEN had a worse prognosis as compared with patients with pure NEC in the small intestine (SI) and appendix, whereas there was no significant survival difference between NEC and MiNEN in the other parts of the GI system. On the whole, age ⩾55 years ( p < 0.0001), male ( p = 0.002), being diagnosed at TNM Stage II–IV ( p < 0.0001) or not receiving surgical treatment ( p < 0.0001) were the independent negative prognostic factors for NEC patients, whereas age ⩾55 years ( p = 0.003), being diagnosed at TNM Stage III–IV ( p < 0.001) or not receiving surgical treatment ( p < 0.001) were identified as the independent negative prognostic factors for the MiNEN patients. Furthermore, when NECs or MiNENs were classified based on the primary tumor site, the results showed that the prognostic factors for NEC and MiNEN varied between the tumor sites. Conclusion: The prognostic differences between NECs and MiNENs in the GI tract are heterogeneous and site-related. Patients with appendiceal or SI MiNEN have a poorer prognosis than patients with pure appendiceal or SI NEC. Therefore, we should pay more attention to patients with MiNEN in the SI and appendix and monitor them more closely.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Do neuroendocrine carcinomas and mixed neuroendocrine–non-neuroendocrine neoplasm of the gastrointestinal tract have the same prognosis? A SEER database analysis of 12,878 cases

Shi

Meng

et al. 2020

Therapeutic Advances in Endocrinology

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show abstract

“…Rectal NENs occur at a high frequency among the Asian population than among white patients. 12 In another study by Amrapurkar DN, an Indian retrospective analysis of GEP-NETs, the most common site of the primary tumor was the stomach (30.2%), followed by the pancreas (23.3%). 13 But in the present study, the duodenum was the most common site of occurrence.…”

Section: Discussionmentioning

confidence: 97%

Immunophenotyping in incidental gastrointestinal neuroendocrine tumors: study at tertiary care centre

et al. 2020

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Background: Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological, biological, and clinical characteristics that have increased in incidence and prevalence in the last few decades. This study is aimed to find out the incidence of neuroendocrine tumors among the gastrointestinal tumors and to grade gastrointestinal neuroendocrine tumors. Materials and Methods: A total of 119 cases of gastrointestinal tumors of gastrointestinal neuroendocrine was included in the study. The paraffin blocks were retrieved and slides were stained with routine Hematoxylin and Eosin, synaptophysin, chromogranin, and Ki67. The histologic grading was done based on mitosis and Ki-67 index as per WHO 2017 classification. Results: Out of 119 cases of Gastrointestinal Tract tumor, 13 (10.92%) constituted neuroendocrine tumors. Duodenum was the most common site (38%) followed by the appendix (23%). The majority (1.9%) of the cases were categorized as of grade 1 followed by 2.3% of grade 2 and 1.19% of grade 3. Immunohistochemically, chromogranin, and synaptophysin were strongly expressed in all ten cases of neuroendocrine tumors. The Ki67 labeling index was <3 % in 10 cases, while it was in the range of 3 – 20 % in 2 cases and >20 % in one case. Conclusions: The incidence of gastrointestinal neuroendocrine tumors is on the rise. They should be considered in developing a differential diagnosis. Hence use of diagnostic modalities such as immunohistochemistry should be implemented for better treatment.

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“…Although ICIs therapy can tremendously improve the survival of patients with various cancers, the proportion of patients who bene t from ICIs is only 10%-30%, and some treated patients have serious immune-related adverse events. Multiple clinical studies have shown that baseline tumor burden is signi cantly associated with poor prognosis and treatment outcomes after immunotherapy [14][15][16].…”

Section: Discussionmentioning

confidence: 99%

High-Baseline Tumor Burden–Associated Macrophages Promote Immunosuppressive Microenvironment and Restrain Immune Checkpoint Inhibitor Efficacy Through the IGFBP2–STAT3–PD-L1 Pathway

Wen

Zhou

Sun

et al. 2022

Preprint

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Background: In recent decades, immune checkpoint inhibitors (ICIs) have become a conspicuous promising treatment. However, there are still some problems such as limited effective rate and undefined suitable patients. With increasing attention to the influence of baseline tumor burden on the therapeutic efficacy of ICIs, most researchers are currently of the view that patients with high-baseline tumor burden (HTB) have shorter overall survival and poor immunotherapy efficacy; nevertheless, recent studies have been limited to clinical phenomena without deep mechanistic exploration. Methods: RNA-seq and Single-cell RNA sequencing were used to reveal the difference of microenvironment between low-baseline tumor burden (LTB) and HTB tumor. Mice model construction, flow cytometry and cytokine antibody array were used to identify the phenomenon and mechanism of HTB effects on tumor immune microenvironment (TIME) and ICIs effcacy.Results: HTB caused a significantly higher infiltration with M2-type macrophages expressing a high level of programmed death-ligand 1 (PD-L1) to block the infiltration by CD8+ T cells and impaired the therapeutic effect of ICIs. HTB-derived IGFBP2 induced the macrophages’ polarization and PD-L1 expression via signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, these HTB–activated macrophages exerted a pro-tumor effect by inhibiting proliferation and cytotoxic function of CD8+ T cells in a PD-L1-dependent fashion. Disappointingly, total tumor burden did not affect the microenvironment or the immunotherapy efficacy of any single tumor. Moreover, macrophage inhibitor in HTB and palliative surgery were not able to increase the therapeutic efficacy in HTB. Only in the early stage of tumor with LTB, the macrophage inhibitor PLX3397 significantly improved the efficacy of ICIs on HTB. Conclusions: Our study has demonstrated that HTB induced the production of PD-L1+ M2-macrophages through the IGFBP2–STAT3 signaling pathway to generate the suppressive TIME, thereby reducing the efficacy of ICIs. These results further clarify the effects and illuminate a novel mechanism of HTB effects on ICI efficacy, and also provide functional evidence for an earlier use of macrophage inhibitors or combination treatment to reshape the tumor microenvironment.

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Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

Cited by 11 publications

References 34 publications

Do neuroendocrine carcinomas and mixed neuroendocrine–non-neuroendocrine neoplasm of the gastrointestinal tract have the same prognosis? A SEER database analysis of 12,878 cases

Do neuroendocrine carcinomas and mixed neuroendocrine–non-neuroendocrine neoplasm of the gastrointestinal tract have the same prognosis? A SEER database analysis of 12,878 cases

Immunophenotyping in incidental gastrointestinal neuroendocrine tumors: study at tertiary care centre

High-Baseline Tumor Burden–Associated Macrophages Promote Immunosuppressive Microenvironment and Restrain Immune Checkpoint Inhibitor Efficacy Through the IGFBP2–STAT3–PD-L1 Pathway

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