bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–03–31
thirteen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. The contribution of the nervous system in the cancer progression.
  2. Sympathetic Nervous Influences Are Negative Prognostic Factors in Stomach Cancer.
  3. Netrin-1 Role in Nociceptive Neuron Sprouting through Activation of DCC Signaling in a Rat Model of Bone Cancer Pain.
  4. Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells.
  5. An algorithmic approach to the management of peripheral nerve tumours.
  6. Acute Macrocystic Thoracic Schwannoma: Systematic Review and Illustrative Case Example.
  7. Schwannoma in the Thenar Eminence: a Case Report.
  8. A Rare Case of Hepatic Schwannoma in the Setting of Schwannomatosis.
  9. Gastric schwannoma: a case report.
  10. Neuropancreatology: The Nervous System and Pain Management in Pancreatic Diseases.
  11. Ascending Colon Schwannoma: A Rare Submucosal Tumour.
  12. Malignant peripheral nerve sheath tumour with divergent epithelioid differentiation in a cat.
  13. Schwannoma of the phrenic nerve. A case report.
  1. BMB Rep. 2024 Mar 25. pii: 6191. [Epub ahead of print]
    The contribution of the nervous system in the cancer progression.
    Hongryeol Park, Chan Hee Lee.
      Cancer progression is driven by genetic mutations, environmental factors, and intricate interactions within the tumor microenvironment (TME). The TME comprises of diverse cell types, such as cancer cells, immune cells, stromal cells, and neuronal cells. These cells mutually influence each other through various factors, including cytokines, vascular perfusion, and matrix stiffness. In the initial or developmental stage of cancer, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor are associated with poor prognosis of various cancers by communicating with cancer cells, immune cells, and peripheral nerves within the TME. Over the past decade, research has been conducted to prevent cancer growth by controlling the activation of neurotrophic factors within tumors, exhibiting a novel attemt in cancer treatment with promising results. More recently, research focusing on controlling cancer growth through regulation of the autonomic nervous system, including the sympathetic and parasympathetic nervous systems, has gained significant attention. Sympathetic signaling predominantly promotes tumor progression, while the role of parasympathetic signaling varies among different cancer types. Neurotransmitters released from these signalings can directly or indirectly affect tumor cells or immune cells within the TME. Additionally, sensory nerve significantly promotes cancer progression. In the advanced stage of cancer, cancer-associated cachexia occurs, characterized by tissue wasting and reduced quality of life. This process involves the pathways via brainstem growth and differentiation factor 15-glial cell line-derived neurotrophic factor receptor alpha-like signaling and hypothalamic proopiomelanocortin neurons. Our review highlights the critical role of neurotrophic factors as well as central nervous system on the progression of cancer, offering promising avenues for targeted therapeutic strategies.
  2. Life (Basel). 2024 Mar 11. pii: 368. [Epub ahead of print]14(3):
    Sympathetic Nervous Influences Are Negative Prognostic Factors in Stomach Cancer.
    Mihai Petrescu, Georgică Târtea, Ion Udriștoiu, Felicia Militaru, Alexandra-Roxana Petrescu, Ana-Maria Ciurea, Ana-Maria Petrescu, Cosmin Obleagă, Cristin Constantin Vere.
      (1) Background: The aim of our study was to assess the involvement of the sympathetic nervous system in the progression of patients with gastric carcinoma by analyzing the sympathetic neuronal fibers and beta 2 adrenoreceptors. (2) Methods: We performed a retrospective study in which we analyzed the clinical, biological, and histological data from a total of 104 patients diagnosed with stomach cancer. (3) Results: After analyzing the immunoreactivity of beta 2 adrenoreceptors, we observed increased values in patients with tumors larger than 5 cm in diameter (p = 0.0371), with a deeper degree of tumor invasion T3-4 (p = 0.0159), invasion in more than two lymph nodes (p = 0.0462), or a TNM stage III-IV. Regarding the survival analysis, better survival rates (65%) were observed for patients with a low value of beta 2 adrenoreceptors (B2A-), compared to B2A (+) patients, in which survival at 3 years of follow-up was only 43%. In addition, the analysis of intra-tumoral sympathetic fibers showed a better survival rate (83%) for patients with a low value of density compared to patients with increased density, in whom the survival rate was only 24%. (4) Conclusions: The findings of this study indicate that patients with stomach cancer have a more unfavorable prognosis when they have a higher density of sympathetic nerve fibers and an increased expression of beta 2 adrenergic receptors inside the tumor.
    Keywords:  prognostic factors; stomach cancer; sympathetic nervous influences
    DOI:  https://doi.org/10.3390/life14030368
  3. J Integr Neurosci. 2024 Feb 27. 23(3): 47
    Netrin-1 Role in Nociceptive Neuron Sprouting through Activation of DCC Signaling in a Rat Model of Bone Cancer Pain.
    Zhihao Gong, Yuxin Zhang, Wei Wang, Xin Li, Kai Wang, Xingji You, Jingxiang Wu.
       BACKGROUND: Bone cancer pain (BCP) is a common primary or metastatic bone cancer complication. Netrin-1 plays an essential role in neurite elongation and pain sensitization. This study aimed to determine the role of netrin-1 from the metastatic bone microenvironment in BCP development and identify the associated signaling pathway for the strategy of BCP management.
    METHODS: The rat BCP model was established by intratibial implantation of Walker 256 cells. Von Frey filaments measured the mechanical pain threshold. Movement-induced pain was assessed using limb use scores. Expressions of associated molecules in the affected tibias or dorsal root ganglia (DRG) were measured by immunofluorescence, immunohistochemistry, real-time quantitative polymerase chain reaction, or western blotting. Transduction of deleted in colorectal cancer (DCC) signaling was inhibited by intrathecal injection of DCC-siRNA.
    RESULTS: In BCP rats, the presence of calcitonin gene-related peptide (CGRP)-positive nerve fibers increased in the metastatic bone lesions. The metastatic site showed enrichment of well-differentiated osteoclasts and expressions of netrin-1 and its attractive receptor DCC. Upregulation of DCC and increased phosphorylation levels of focal adhesion kinase (FAK) and Rac family small GTPase 1/Cell division cycle 42 (Rac1/Cdc42) were found in the DRG. Intrathecal administration of DCC-siRNA led to a significant reduction in FAK and Rac1/Cdc42 phosphorylation levels in the DRG, decreased nociceptive nerve innervation, and improved pain behaviors.
    CONCLUSIONS: Netrin-1 may contribute to the activation of the BCP by inducing nociceptive nerve innervation and improving pain behaviors.
    Keywords:  CGRP; DCC; FAK; Rac1/Cdc42; axonal guidance; bone cancer pain; netrin-1; neurite elongation; nociception
    DOI:  https://doi.org/10.31083/j.jin2303047
  4. J Clin Med. 2024 Mar 20. pii: 1785. [Epub ahead of print]13(6):
    Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells.
    Ingrid Garajová, Francesca Trentini, Francesco Leonardi, Elisa Giovannetti.
      Pancreatic ductal adenocarcinoma is one of the most lethal solid malignancies, characterized by its aggressiveness and metastatic potential, with a 5-year survival rate of only 13%. Progress in the management of metastatic disease has been modest. A robust connection between nervous system and tumor progression exists, with prominent neural alterations having been observed during pancreatic cancer's progression, including neural hypertrophy, neural density, and neural remodeling. The pancreatic tumor microenvironment includes s set of cells and structures that constantly dialogue with cancer cells, influencing its growth and behavior. The microglia is key cellular components of the tumor microenvironment, and Schwann cells are the principal glial cells in the peripheral neural system. Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting a variety of factors and can support a tumor's invasion of nerves and distant metastasis, with further pain exacerbation. Schwann cells secrete various pain-related molecules, such as the neural growth factor, to mediate the activation of primary sensory neurons, leading to pain induction. The binding of the neural growth factor to tropomyosin receptor kinase A is an important signaling mechanism for pain perception in humans. Consequently, directing efforts towards targeting neural invasion may provide an alternative strategy to improve the prognosis of and alleviate pain in patients with pancreatic cancer.
    Keywords:  Schwann cells; cancer pain; neural invasion; pancreatic ductal adenocarcinoma; tumor microenvironment
    DOI:  https://doi.org/10.3390/jcm13061785
  5. J Hand Surg Eur Vol. 2024 Mar 27. 17531934241238739
    An algorithmic approach to the management of peripheral nerve tumours.
    Tim Hems, Antonina Parafioriti, Binu P Thomas, Andrea Di Bernardo.
      This article reviews the pathology and management of peripheral nerve tumours, including a framework for investigation and decision-making. Most tumours are benign, including schwannomas and neurofibromas, but malignant peripheral nerve sheath tumours can occur. The risk of malignant change is remote for schwannomas but higher for neurofibromas, particularly in neurofibromatosis type 1. Magnetic resonance imaging is useful for defining the relationship of a swelling with adjacent nerves but is not definitive for tissue diagnosis. Increasing size, pain and neurological deficit suggest malignant change and TruCut needle biopsy is indicated, although there is a risk of sampling error. Excision biopsy preserving nerve function may be carried out for benign tumours to relieve symptoms. Malignant tumours require a multidisciplinary approach. Complete surgical excision with clear margins is the only curative treatment and may be supplemented with radiotherapy and chemotherapy. However, prognosis remains poor, particularly for patients with neurofibromatosis.
    Keywords:  Schwannoma; malignant peripheral nerve sheath tumour; neurofibroma; pathology; treatment
    DOI:  https://doi.org/10.1177/17531934241238739
  6. World Neurosurg. 2024 Mar 22. pii: S1878-8750(24)00468-6. [Epub ahead of print]
    Acute Macrocystic Thoracic Schwannoma: Systematic Review and Illustrative Case Example.
    Grace R Fassina, Spencer J Oslin, Helen H Shi, John F Burke, Caple A Spence, Christopher S Graffeo.
       BACKGROUND: Schwannomas are benign peripheral nerve sheath tumors arising from myelinating Schwann cells. Although macrocystic changes are regularly encountered in schwannoma variants such as vestibular nerve tumors, they are exceedingly rare among spinal neoplasms.
    METHODS: Case report and systematic review of four databases (Ovid Medline, PubMed, Science Direct, and SCOPUS) from inception to present. All peer-reviewed publications reporting intradural cystic thoracic schwannoma were included.
    RESULTS: We identified 8 publications documenting 9 cases of cystic thoracic schwannoma. Four were female, five male; median age was 41 years (range, 27-80). Presentations ranged from incidental to pain, sensory changes, lower extremity paresis, or bowel/bladder dysfunction. Characteristic radiographic findings included T1 hypointensity, T2 hyperintensity, and cord effacement or compression. The present case followed a similar pattern: a 52-year-old male presented with worsening bilateral lower extremity weakness, low back pain, and gait dysfunction, worsening over three days. Examination also revealed decreased left lower extremity sensation. Imaging identified a well-delineated intradural, extramedullary macrocystic extending over T7-T10. The patient underwent a laminectomy resulting in complete tumor resection and restoration of intact neurological function. Final pathology confirmed benign cystic schwannoma.
    CONCLUSION: Macrocystic thoracic schwannomas are exceedingly rare, and lack a comprehensive scheme for clinical classification of their natural history and pathogenesis. We report the 10th case of such a schwannoma, and the first associated systematic review. Although macrocystic thoracic schwannomas are not frequently encountered, accurate diagnosis and appropriate neurosurgical treatment is critical in these vulnerable patients, given the opportunity for excellent functional outcomes following neurosurgical treatment.
    Keywords:  Acute Macrocystic; Thoracic Cystic Schwannoma
    DOI:  https://doi.org/10.1016/j.wneu.2024.03.091
  7. Indian J Surg Oncol. 2024 Mar;15(Suppl 1): 148-151
    Schwannoma in the Thenar Eminence: a Case Report.
    J Terrence Jose Jerome, N Mohammed Sagy.
      This report describes a rare presentation of schwannoma in the thenar aspect of a surgeon and reviews the literature. A 35-year-old surgeon had a slow-growing swelling in his left thenar eminence. Clinical and radiological findings suggested it was a well-encapsulated mass within the abductor pollicis brevis muscle. A complete surgical excision was done, and the histopathological findings confirmed schwannoma, a benign peripheral nerve tumor. The surgeon remained symptom-free and had no recurrence at 1 year of follow-up. Though a benign peripheral nerve tumor is rare in the hand, it remains one of the differential diagnoses for a thenar eminence swelling. Surgical enucleation preserving the nerve fascicles achieves an excellent functional outcome.
    Keywords:  Abductor pollicis brevis muscle; Good outcome; Peripheral nerve tumor; Schwannoma; Thenar eminence
    DOI:  https://doi.org/10.1007/s13193-024-01911-3
  8. Cureus. 2024 Feb;16(2): e54705
    A Rare Case of Hepatic Schwannoma in the Setting of Schwannomatosis.
    Minh-Anh Le, Rachel Shi, Justin Geraghty, Vania Zayat, Jignesh Parikh.
      Schwannomas are benign nerve sheath tumors commonly found in the head, neck, vestibular system, and extremities. Primary hepatic schwannomas are exceptionally rare, with 34 cases reported to date according to our review of the literature. This case report describes a 79-year-old man with a medical history of skin and thyroid cancer, who presented with no clinical symptoms and underwent a follow-up MRI due to an initial scan indicating a suspicious hepatic mass resembling an atypical hemangioma. The MRI revealed a 3.6 cm left hepatic mass concerning for an intrahepatic cholangiocarcinoma. Histopathological and immunohistochemical studies of a biopsy of the liver mass confirmed the presence of a benign hepatic schwannoma. Further evaluation revealed multiple spinal schwannomas, leading to the diagnosis of schwannomatosis. The diagnosis of hepatic schwannomas poses challenges through imaging alone. This case underscores the importance of microscopic evaluation in accurately diagnosing hepatic masses. Additionally, the presence of concurrent schwannomas should be considered in patients initially diagnosed with isolated schwannomas.
    Keywords:  hepatic schwannoma; neurofibromatosis; schwannoma; schwannomatosis; spinal schwannoma
    DOI:  https://doi.org/10.7759/cureus.54705
  9. J Surg Case Rep. 2024 Mar;2024(3): rjae181
    Gastric schwannoma: a case report.
    Ognen Kostovski, Gjorgji Trajkovski, Gligor Ristovski, Slavica Kostadinova Kunovska, Irena Kostovska.
      Gastric schwannomas are rare mesenchymal tumors that arise from the intestinal nerve plexuses. They present with nonspecific symptoms and are often discovered incidentally. We present the case of a 68-year-old patient who had been suffering from abdominal discomfort for 6 months. After a complete examination, including abdominal computed tomography and upper gastrointestinal endoscopy, we discovered a submucosal gastric lesion with benign gross features without evidence of lymph node or metastatic involvement. He underwent an open laparotomy. Final pathohistological and immunohistochemically identification of the surgical specimen established the diagnosis of benign schwannoma. Considering the excellent prognosis of the tumor, no adjuvant treatment was suggested other than simple clinical monitoring every 6 months. Despite the accessibility of advanced endoscopy and imaging techniques, the diagnosis of gastric schwannoma is rarely made preoperatively. In the latter case, the best treatment is still complete excision with wide margins.
    Keywords:  gastric schwannoma; immunohistochemistry; rare gastric tumors
    DOI:  https://doi.org/10.1093/jscr/rjae181
  10. Life (Basel). 2024 Feb 23. pii: 299. [Epub ahead of print]14(3):
    Neuropancreatology: The Nervous System and Pain Management in Pancreatic Diseases.
    Alberto Nicoletti, Federica Vitale, Mattia Paratore, Giuseppe Quero, Marcantonio Negri, Enrico Celestino Nista, Sergio Alfieri, Antonio Gasbarrini, Lorenzo Zileri Dal Verme.
      The intricate network of the pancreatic nervous system plays a fundamental role in physiologic functions of the endocrine and exocrine pancreas. Several pancreatic diseases affect the normal functionality of the pancreatic nervous system. This chronic derangement leads to anatomical alterations, such as neural hypertrophy and increased nerve density. Perineural invasion is a prominent feature of pancreatic cancer, contributing to cancer progression and metastasis. Despite the fact that these pathogenic mechanisms are still incompletely studied and understood, the constant occurrence of these alterations highlights their importance in the pathophysiology of the pancreatic diseases. The occurrence of anatomical changes is strictly linked to the appearance of pain. Pancreatic pain has peculiar features, and its management is complex in clinical practice. In the present review, the evidence on lifestyle, pharmacological and interventional approaches for the management of pancreatic pain is presented. Analgesic therapy is the cornerstone of pain treatment. However, it is important to identify the individual characteristic of the patients and personalize the approach to pain management. Nevertheless, the incomplete efficacy of these strategies makes this field an area of unmet needs. The study of neuroplasticity is crucial to understand the mechanisms that regulate the pathophysiology of pancreatic diseases. Several trials testing new drugs with specific neuromodulatory effects are ongoing. However, further studies are needed to investigate crucial targets to develop novel therapies for the modulation of the nervous system and the prevention of complications of pancreatic diseases. This comprehensive review summarizes the importance of the nervous system in pancreatic diseases with a special focus on its anatomy and physiology, its pathophysiological features and clinical relevance in pancreatic disease, the treatment of pancreatic pain, and the identification of future trends of research.
    Keywords:  acute pancreatitis; chronic pancreatitis; neural plasticity; neuromodulation; pancreatic cancer; pancreatic nervous system; pancreatic pain; personalized medicine
    DOI:  https://doi.org/10.3390/life14030299
  11. Cureus. 2024 Feb;16(2): e54902
    Ascending Colon Schwannoma: A Rare Submucosal Tumour.
    Kugendran Ponniah, Larissa Yong, Abdul Rana, Christopher McDonald.
      We present a rare case of schwannoma in the ascending colon of a 60-year-old female with dyslipidemia. A series of diagnostic procedures, including colonoscopy and CT colonography, led to the successful robotic-assisted right hemicolectomy. Histological and immunohistochemical analyses confirmed the diagnosis of schwannoma, and the patient achieved a complete recovery post-surgery.
    Keywords:  ascending colon; diagnosis; histology; immunohistochemistry; schwannoma
    DOI:  https://doi.org/10.7759/cureus.54902
  12. J Comp Pathol. 2024 Mar 26. pii: S0021-9975(24)00029-X. [Epub ahead of print]210 25-28
    Malignant peripheral nerve sheath tumour with divergent epithelioid differentiation in a cat.
    Francisco Rodríguez Guisado.
      Divergent differentiation, mainly towards various subsets of mesenchymal cells, is encountered sporadically in human malignant peripheral nerve sheath tumours (MPNSTs) but this is the first report of epithelioid components within this neoplasm in a cat. An 8-year-old, spayed female Domestic Shorthaired cat was presented for surgical removal of a subcutaneous mass on the right flank. Morphological and immunohistochemical analysis revealed a malignant neoplasm with spindloid cells intermixed with an epithelioid component that had squamous differentiation. There was intense immunolabelling of vimentin, S100 protein, neuron-specific enolase, laminin and glial fibrillary acidic protein in the spindloid cell component and for cytokeratin (CK) AE1/AE3 and CK5/6 in the epithelial elements. Melanoma-associated antigen, desmin, α-smooth muscle actin, CD18, CD31, ionized calcium binding adapter molecule-1 and CK8/18 were not expressed, which helped differentiate the tumour from other feline spindloid cell neoplasms. These features are characteristic of divergent epithelioid differentiation of MPNST.
    Keywords:  cat; epithelioid differentiation; immunohistochemistry; peripheral nerve sheath tumour
    DOI:  https://doi.org/10.1016/j.jcpa.2024.02.007
  13. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024 Mar 27.
    Schwannoma of the phrenic nerve. A case report.
    Josef Chudacek, Tomas Bohanes, Marek Szkorupa, Martin Stasek, Jan Hanuliak, Daniela Skanderova, Dusan Klos.
       BACKGROUND: Neurogenic tumors are the third most common tumors occurring within the mediastinum. Predominantly completely asymptomatic, they are most often found in the posterior mediastinum, although they may also be located, albeit rarely, in the middle mediastinum. Thus, in the cases of tumors localized in the middle mediastinum, schwannomas of the phrenic nerve must always be considered.
    CASE REPORT: In this case, a male patient presented with a tumor of the middle mediastinum. PET/CT scan determined that it was a circumscribed tumor without signs of dissemination. However, due to the tumor's location, a preoperative biopsy of the tumor was not possible. Therefore, the patient underwent videothoracoscopic extirpation of the tumor, including the necessary resection of the phrenic nerve that passed through the centre of the tumor. Subsequent histological analysis definitively confirmed a schwannoma with low proliferative activity.
    CONCLUSIONS: Differential diagnosis of mediastinal tumours is very difficult; however, in the case of circumscribed tumours not invading the surrounding tissues, proceeding to surgical revision, with the complete removal of the tumour, is possible, even without determining the histological nature. Minimally invasive surgical techniques dominate the treatment of neurogenic tumors of the mediastinum; they are associated with minimal complications and allow a rapid return of the patient to their normal activities.
    Keywords:  mediastinum; nervus phrenius; neurogenic tumors; schwannom; videothoracoscopic resection
    DOI:  https://doi.org/10.5507/bp.2024.011
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