bims-netuvo 2024-01-21 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–01–21
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Letter to the Editor: Terminology of intraneural invasion, perineural invasion and perineural spread.
Microglia contribute to mammary tumor-induced neuroinflammation in a female mouse model.
Microglia Promote Inhibitory Synapse Phagocytosis in the Spinal Cord Dorsal Horn and Modulate Pain-Like Behaviors in a Murine Cancer-Induced Bone Pain Model.
Increased sympathetic nervous system impairs prognosis in lung cancer patients: a scoping review of clinical studies.
Predictive Factors Associated With Survival in Periampullary Cancers Following Pancreaticoduodenectomy: A Retrospective Analysis.
Systematic characterization of the clinical and pathological features of schwannomas harboring SH3PXD2A::HTRA1 fusion.
Shaping our understanding of malignant peripheral nerve sheath tumor: a bibliometric analysis of the 100 most-cited articles.
Prediction of the lymphatic, microvascular, and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging.

World Neurosurg. 2024 Jan;pii: S1878-8750(23)01492-4. [Epub ahead of print]181 196-198

Letter to the Editor: Terminology of intraneural invasion, perineural invasion and perineural spread.

Stepan Capek, R Shane Tubbs, Robert J Spinner.

DOI: https://doi.org/10.1016/j.wneu.2023.10.086
FASEB J. 2024 Jan 31. 38(2): e23419

Microglia contribute to mammary tumor-induced neuroinflammation in a female mouse model.

Lindsay D Strehle, Lauren D Otto-Dobos, Corena V Grant, Erica R Glasper, Leah M Pyter.

  Following diagnosis but before treatment, up to 30% of breast cancer patients report behavioral side effects (e.g., anxiety, depression, memory impairment). Our rodent mammary tumor model recapitulates aspects of these behavioral sequelae, as well as elevated circulating and brain inflammatory mediators. Neuroinflammation is a proposed mechanism underlying the etiology of mood disorders and cognitive deficits, and therefore may be contributing to tumor-associated behavioral side effects. The cellular mechanisms by which tumor-induced neuroinflammation occurs remain unknown, making targeted treatment approaches inaccessible. Here, we tested the hypotheses that microglia are the primary cells driving tumor-induced neuroinflammation and behavioral side effects. Young adult female BALB/c mice were induced with a 67NR mammary tumor; tumor-free controls underwent a sham surgery. Mammary tumors increased IBA1+ and GFAP+ staining in the amygdala and hippocampus relative to tumor-free controls. However, tumors did not alter gene expression of Percoll-enriched microglia isolated from the whole brain. While cognitive, social, and anhedonia-like behaviors were not altered in tumor-bearing mice, tumors increased central tendency in the open-field test; microglia depletion did not reverse this effect. Brain region RT-qPCR data indicated that microglia depletion attenuated tumor-induced elevations of neuroinflammatory gene expression in a region- and mediator-specific manner. These results indicate a causal role of microglia in tumor-induced neuroinflammation. This research advances our understanding of the cellular mechanisms underlying tumor-induced neuroinflammation in order to understand how brain responses (e.g., behavior) may be altered with subsequent cancer-related immune challenges.

Keywords:  amygdala; astrocytes; brain; cancer; cytokine; hippocampus

DOI:  https://doi.org/10.1096/fj.202301580RR
Anesth Analg. 2024 Jan 19.

Microglia Promote Inhibitory Synapse Phagocytosis in the Spinal Cord Dorsal Horn and Modulate Pain-Like Behaviors in a Murine Cancer-Induced Bone Pain Model.

Zuoxia Zhang, Yanting Mao, Simin Huang, Rui Xu, Yulin Huang, Shuming Li, Yu'e Sun, Xiaoping Gu, Zhengliang Ma.

BACKGROUND: The microglial activation has been implicated in cancer-induced bone pain. Recent studies have revealed that microglia mediate synaptic pruning in the central nervous system, where the cluster of differentiation 47-signal regulatory protein α (CD47-SIRPα) axis creates a "don't eat me" signal and elicits an antiphagocytic effect to protect synapses against elimination. To date, the synaptic phagocytosis in microglia has never been investigated in the murine cancer-induced bone pain model. The present experiments sought to explore whether microglia phagocytize synapses in mice with bone cancer pain as well as the possible mechanisms.
METHODS: Male C3H/HeN mice were used to induce bone cancer pain. Minocycline and S-ketamine were injected into D14. The number of spontaneous flinches (NSF) and paw withdrawal mechanical thresholds (PWMT) were measured on D0, D4, D7, D10, D14, D21, and D28. Hematoxylin and eosin staining presented bone lesions. Western blotting examined the Gephyrin, CD47, and SIRPα expression. Flow cytometry evaluated the proportion of SIRPα+ cells in the spine. Immunofluorescence and 3-dimensional reconstruction showed the Gephyrin puncta inside microglial lysosomes.
RESULTS: Mice embedded with tumor cells induced persistent spontaneous pain and mechanical hyperalgesia. Hematoxylin and eosin staining revealed bone destruction and tumor infiltration in marrow cavities. Microglia underwent a responsive and proliferative burst (t = -16.831, P < .001). Western blotting manifested lowered Gephyrin expression in the tumor group (D4, D7, D10, D14, D21, and D28: P < .001). Immunofluorescence and 3-dimensional reconstruction showed larger volumes of Gephyrin puncta inside microglial lysosomes (t = -23.273, P < .001; t = -27.997, P < .001). Treatment with minocycline or S-ketamine exhibited pain relief and antiphagocytic effects (t = -6.191, P < .001, t = -7.083, P < .001; t = -20.767, P < .001, t = -17.080, P < .001; t = 11.789, P < .001, t = 16.777, P < .001; t = 8.868, P < .001, t = 21.319, P < .001). Last but not least, the levels of CD47 and SIRPα proteins were downregulated (D10: P = .004, D14, D21, and D28: P < .001; D10, D14, D21, and D28: P < .001). Flow cytometry and immunofluorescence substantiated reduced microglial SIRPα (t = 11.311, P < .001; t = 12.189, P < .001).
CONCLUSIONS: Microglia-mediated GABAergic synapse pruning in the spinal cord dorsal horn in bone cancer pain mice, which might be associated with the declined CD47-SIRPα signal. Our research uncovered an innovative mechanism that highlighted microglia-mediated synaptic phagocytosis in a murine cancer-induced bone pain model.

DOI: https://doi.org/10.1213/ANE.0000000000006824
Lung Cancer Manag. 2023 Dec;12(4): LMT63

Increased sympathetic nervous system impairs prognosis in lung cancer patients: a scoping review of clinical studies.

Fabrício T Garramona, Telma F Cunha, Janaína S Vieira, Gabriela Borges, Gabriela Santos, Gilberto de Castro, Carlos Ugrinowitsch, Patrícia C Brum.

   Aim: To summarize current knowledge, gaps, quality of the evidence and show main results related to the role of the autonomic nervous system in lung cancer.
Methods: Studies were identified through electronic databases (PubMed, Scopus, Embase and Cochrane Library) in October 2023, and a descriptive analysis was performed. Twenty-four studies were included, and most were observational.
Results: Our data indicated an increased expression of β-2-adrenergic receptors in lung cancer, which was associated with poor prognosis. However, the use of β-blockers as an add-on to standard treatment promoted enhanced overall survival, recurrence-free survival and reduced metastasis occurrence.
Conclusion: Although the results herein seem promising, future research using high-quality prospective clinical trials is required to draw directions to guide clinical interventions.

Keywords:  lung cancer; non-small-cell lung carcinoma; parasympathetic; small cell lung carcinoma; sympathetic

DOI:  https://doi.org/10.2217/lmt-2023-0006
Cureus. 2023 Dec;15(12): e50607

Predictive Factors Associated With Survival in Periampullary Cancers Following Pancreaticoduodenectomy: A Retrospective Analysis.

Narendra Maharjan, Ramesh Singh Bhandari, Paleswan Joshi Lakhey.

  Background Periampullary cancers arise from four different anatomical sites and are in close proximity. But they have different survival outcomes. There are various clinicopathological factors associated with survival after pancreaticoduodenectomy done for periampullary cancers. So, we aimed to identify the predictive factors associated with poor survival in periampullary cancers at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Methods We analyzed the medical records of patients who underwent pancreaticoduodenectomy (PD) at Tribhuvan University Teaching Hospital, Kathmandu, from April 2004 to May 2014. Demography, clinicopathological features, and survival outcomes were analyzed retrospectively. Results This study included 61 patients. The mean age of patients was 56.2 ± 14.2 years, and there was a male preponderance (M:F = 1.4). The median survival of all patients was 24 months. Non-pancreatic periampullary cancer patients had better median survival as compared to pancreatic cancer patients (24 vs. 8 months, p = 0.03). The presence of lymphovascular invasion (LVI), peripheral invasion (PNI), nodal involvement, and a higher lymph node ratio (LNR) were associated with poor median survival. However, perineural invasion was the only factor associated with poor survival in multivariate analysis. Conclusion The presence of perineural invasion is associated with poor survival outcomes in patients with periampullary cancer following pancreaticoduodenectomy. Also, carcinoma of the head of the pancreas has poor survival as compared to other periampullary cancers.

Keywords:  ampullary carcinoma; pancreatic carcinoma; pancreaticoduodenectomy; periampullary carcinoma; predictive factor

DOI:  https://doi.org/10.7759/cureus.50607
Mod Pathol. 2024 Jan 12. pii: S0893-3952(24)00007-3. [Epub ahead of print] 100427

Systematic characterization of the clinical and pathological features of schwannomas harboring SH3PXD2A::HTRA1 fusion.

Jen-Chieh Lee, Pei-Hang Lee, Sung-Chou Li, Kuan-Cho Liao, Yi-Ming Chang, Hui-Chun Chen, Yu-Chien Kao, Pao-Shu Wu, Shih-Chiang Huang, Jen-Wei Tsai, Chia-Fa Hu, Chih-Hao Li, Ting-Ting Liu, Shih-Chen Yu, Jui-Chu Wang, Hsuan-Ying Huang.

  The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using RT-PCR. Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 non-schwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≧10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity: 0.950; specificity: 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

Keywords:  SH3PXD2A::HTRA1 fusion; peripheral nerve sheath tumor; schwannoma

DOI:  https://doi.org/10.1016/j.modpat.2024.100427
World Neurosurg. 2024 Jan 12. pii: S1878-8750(24)00066-4. [Epub ahead of print]

Shaping our understanding of malignant peripheral nerve sheath tumor: a bibliometric analysis of the 100 most-cited articles.

Julian S Rechberger, Elena Millesi, Erica A Power, Huan Wang, Samir Mardini, Robert J Spinner, David J Daniels.

   BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas of mesenchymal origin, characterized by a heterogeneous pathological spectrum, limited therapeutic options, and high metastatic potential.
METHODS: Here, the authors conducted a comprehensive bibliometric analysis of the 100 most-cited MPNST articles by utilizing Elsevier's Scopus to identify all relevant published and indexed articles referring to MPNST, thereby aiming to elucidate the pertinent research findings regarding the disease's pathophysiology and therapeutic advancements. Articles were classified as basic science (BSc) or clinical (CL) and analyzed for various bibliometric parameters.
RESULTS: The majority of articles (75%) focused on clinical aspects, reflecting the extensive clinicopathological characterization of MPNSTs. Notable studies investigated prognostic factors, histological and immunohistochemical features, and diagnostic modalities. The identification of loss of function mutations in the Polycomb repressive complex 2 (PRC2) emerged as a pivotal role, as it opened avenues for potential targets for novel therapeutic interventions. Newer articles (published in or after 2006) demonstrated higher citation rates, suggesting evolving impact and collaboration.
CONCLUSIONS: This bibliometric analysis showed how developments in the understanding of MPNST pathophysiology and the creation of novel therapeutic strategies occurred throughout time. Changes that have been noticed recently could portend future innovative therapeutic approaches.

Keywords:  Bibliometric analysis; Citation analysis; Impactful; MPNST; Malignant peripheral nerve sheath tumor; Most-cited

DOI:  https://doi.org/10.1016/j.wneu.2024.01.054
World J Gastrointest Surg. 2023 Dec 27. 15(12): 2809-2819

Prediction of the lymphatic, microvascular, and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging.

Yu-Liang Liu, Hai-Bin Zhu, Mai-Lin Chen, Wei Sun, Xiao-Ting Li, Ying-Shi Sun.

   BACKGROUND: Significant correlation between lymphatic, microvascular, and perineural invasion (LMPI) and the prognosis of pancreatic neuroendocrine tumors (PENTs) was confirmed by previous studies. There was no previous study reported the relationship between magnetic resonance imaging (MRI) parameters and LMPI.
AIM: To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs (NFPNETs).
METHODS: A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study. The patients were divided into group 1 (n = 34, LMPI negative) and group 2 (n = 27, LMPI positive). The clinical characteristics and qualitative MRI features were collected. In order to predict LMPI status in NF-PNETs, a multivariate logistic regression model was constructed. Diagnostic performance was evaluated by calculating the receiver operator characteristic (ROC) curve with area under ROC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.
RESULTS: There were significant differences in the lymph node metastasis stage, tumor grade, neuron-specific enolase levels, tumor margin, main pancreatic ductal dilatation, common bile duct dilatation, enhancement pattern, vascular and adjacent tissue involvement, synchronous liver metastases, the long axis of the largest lymph node, the short axis of the largest lymph node, number of the lymph nodes with short axis > 5 or 10 mm, and tumor volume between two groups (P < 0.05). Multivariate analysis showed that tumor margin (odds ratio = 11.523, P < 0.001) was a predictive factor for LMPI of NF-PNETs. The area under the receiver value for the predictive performance of combined predictive factors was 0.855. The sensitivity, specificity, PPV, NPV and accuracy of the model were 48.1% (14/27), 97.1% (33/34), 97.1% (13/14), 70.2% (33/47) and 0.754, respectively.
CONCLUSION: Using preoperative MRI, ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Keywords:  Lymphatic invasion; Magnetic resonance imaging; Microvascular invasion; Pancreatic neuroendocrine tumors; Perineural invasion

DOI:  https://doi.org/10.4240/wjgs.v15.i12.2809