bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–05–28
twelve papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Neurotransmitters: promising immune modulators in the tumor microenvironment.
  2. Neural induction drives body axis formation during embryogenesis, but a neural induction-like process drives tumorigenesis in postnatal animals.
  3. Pleural Schwannoma Presenting As Musculoskeletal Type Pain: A Case Report.
  4. Prognostic predictors for recurrence following curative resection in grade I/II pancreatic neuroendocrine tumours.
  5. Expression of Ras signaling pathway proteins and developmental factors in peripheral nerve sheath tumors of patients with neurofibromatosis type 1.
  6. Schwann cells as a target cell for the treatment of cancer pain.
  7. Development and Validation of a Machine-Learning Model to Predict Early Recurrence of Intrahepatic Cholangiocarcinoma.
  8. Editorial: Feline tumors of nervous system.
  9. Schwannoma of Posterior Interosseous Nerve: A Case Report and Review of Literature.
  10. Primary Cardiac Schwannoma: A Meta-Analysis of Individual Case Reports.
  11. Bronchial Schwannoma Incidentally Discovered via Bronchoscopy: A Case Report.
  12. Sciatica Caused by Perineural Spread of Prostate Cancer.
  1. Front Immunol. 2023 ;14 1118637
    Neurotransmitters: promising immune modulators in the tumor microenvironment.
    Luxi Xiao, Xunjun Li, Chuanfa Fang, Jiang Yu, Tao Chen.
      The tumor microenvironment (TME) is modified by its cellular or acellular components throughout the whole period of tumor development. The dynamic modulation can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Hence, the focus of cancer research and intervention has gradually shifted to TME components and their interactions. Accumulated evidence indicates neural and immune factors play a distinct role in modulating TME synergistically. Among the complicated interactions, neurotransmitters, the traditional neural regulators, mediate some crucial regulatory functions. Nevertheless, knowledge of the exact mechanisms is still scarce. Meanwhile, therapies targeting the TME remain unsatisfactory. It holds a great prospect to reveal the molecular mechanism by which the interplay between the nervous and immune systems regulate cancer progression for laying a vivid landscape of tumor development and improving clinical treatment.
    Keywords:  cancer immunology; immune modulator; neuroimmune interaction; neurotransmitter; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2023.1118637
  2. Front Cell Dev Biol. 2023 ;11 1092667
    Neural induction drives body axis formation during embryogenesis, but a neural induction-like process drives tumorigenesis in postnatal animals.
    Ying Cao.
      Characterization of cancer cells and neural stem cells indicates that tumorigenicity and pluripotency are coupled cell properties determined by neural stemness, and tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. Neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells lose their epidermal fate and assume the neural default fate and consequently, turn into neuroectodermal cells. They further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or a conjoined twin. During tumorigenesis, cells progressively lose their original cell identity and gain of neural stemness, and consequently, gain of tumorigenicity and pluripotency, due to various intra-/extracellular insults in cells of a postnatal animal. Tumorigenic cells can be induced to differentiation into normal cells and integrate into normal embryonic development within an embryo. However, they form tumors and cannot integrate into animal tissues/organs in a postnatal animal because of lack of embryonic inducing signals. Combination of studies of developmental and cancer biology indicates that neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal. Tumorigenicity is by nature the manifestation of aberrant occurrence of pluripotent state in a postnatal animal. Pluripotency and tumorigenicity are both but different manifestations of neural stemness in pre- and postnatal stages of animal life, respectively. Based on these findings, I discuss about some confusion in cancer research, propose to distinguish the causality and associations and discriminate causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research.
    Keywords:  body axis formation; epithelial-mesenchymal transition; neural induction; neural stemness; pluripotency; tumor microenvironment; tumorigenesis; tumorigenicity
    DOI:  https://doi.org/10.3389/fcell.2023.1092667
  3. Cureus. 2023 Apr;15(4): e37771
    Pleural Schwannoma Presenting As Musculoskeletal Type Pain: A Case Report.
    Ali El-Husari, Hozaifa Tabbaa, Mohamed Ibrahim, Davong D Phrathep, Abubakr Bajwa.
      Schwannomas are benign peripheral nerve sheath tumors typically found in the neck, flexor surfaces of the extremities, mediastinum, posterior spinal roots, cerebellopontine angle, and retroperitoneum. Pleural schwannomas are a type of neoplasm that arises from autonomic nerve fiber sheaths in the pleura and rarely originate in the thoracic cavity. These schwannomas tend to be asymptomatic, benign, and slow-growing neoplasms. Although pleural schwannomas commonly occur in males, our report highlights a unique presentation of a pleural schwannoma presenting as musculoskeletal-type chest pain in an adult female. Our patient's diagnosis of pleural schwannoma was supported after X-Ray, Computed Tomography (CT) Scan, and Positron Emission Tomography (PET) Scan imaging was complete. All imagining and immunohistochemical staining yielded pleural schwannoma as the final diagnosis. We aim to bring awareness to the necessity of imaging and histopathological staining in atypical clinical cases of pleural schwannoma. Our novel case highlights pleural schwannoma as a differential diagnosis for patients with intermittent, musculoskeletal-type chest pain.
    Keywords:  benign peripheral nerve sheath tumor; intermittent chest pain; pleural schwannoma; rare benign tumor; s100 
    DOI:  https://doi.org/10.7759/cureus.37771
  4. Langenbecks Arch Surg. 2023 May 22. 408(1): 204
    Prognostic predictors for recurrence following curative resection in grade I/II pancreatic neuroendocrine tumours.
    Amit Chopde, Amit Gupta, Vikram Chaudhari, Rahul Parghane, Sandip Basu, Vikas Ostwal, Anant Ramaswamy, Ameya Puranik, Shailesh V Shrikhande, Manish S Bhandare.
       INTRODUCTION: Pancreatic neuroendocrine tumours (pNETs) have an excellent long-term survival after resection, but are associated with a high recurrence rate. Identification of prognostic factors affecting recurrences would enable identifying subgroup of patients at higher risk of recurrences, who may benefit from more aggressive treatment.
    METHODS: A retrospective analysis of prospectively maintained database of patients undergoing pancreatectomy with curative intent for grade I and II pNETs between July 2007 and June 2021 was performed. Perioperative and long-term outcomes were analysed.
    RESULTS: A total of 68 resected patients of pNETs were included in this analysis. Fifty-two patients (76.47%) underwent pancreaticoduodenectomy, 10 (14.7%) patients had distal pancreatectomy, and 2 (2.9%) patients underwent median pancreatectomy, while enucleation was performed in 4 patients (5.8%). The overall major morbidity (Clavien-Dindo III/IV) and mortality rates were 33.82% and 2.94%, respectively. At a median follow-up period of 48 months, 22 (32.35%) patients had disease recurrence. The 5-year overall survival and 5-year recurrence-free survival (RFS) rates were 90.2% and 60.8%, respectively. While OS was unaffected by different prognostic factors, multivariate analysis showed that lymph node involvement, Ki-67 index ≥5%, and presence of perineural invasion (PNI) were independently associated with recurrence.
    CONCLUSIONS: While surgical resection gives excellent overall survival in grade I/II pNETs, lymph node positivity, higher Ki-67 index, and PNI are associated with a high risk for recurrence. Patients with these characteristics should be stratified as high risk and evaluated for more intensive follow-up and aggressive treatment strategies in future prospective studies.
    Keywords:  GEP-NETs; Pancreatic neuroendocrine tumours; Recurrence of pNETs; pNETs
    DOI:  https://doi.org/10.1007/s00423-023-02943-z
  5. Clin Neuropathol. 2023 May 25.
    Expression of Ras signaling pathway proteins and developmental factors in peripheral nerve sheath tumors of patients with neurofibromatosis type 1.
    Christian Hagel, Louisa K N Nörnberg, Reinhard E Friedrich.
       PURPOSE: To characterize expression of factors relevant for Ras signaling and developmental factors in a large series of peripheral nerve sheath tumors (PNST) obtained from patients with neurofibromatosis type 1 (NF1).
    MATERIALS AND METHODS: Tissue micro-array technique was applied to study 520 PNST of 385 NF1 patients by immunohistochemistry for mTor, Rho, phosphorylated MEK, Pax7, Sox9, and periaxin expression. PNST comprised cutaneous neurofibroma (CNF) (n = 114), diffuse neurofibroma (DNF) (n = 109), diffuse plexiform neurofibroma (DPNF) (n = 108), plexiform neurofibroma (PNF) (n = 110), and malignant PNST (MPNST) (n = 22).
    RESULTS: All proteins examined showed highest expression levels/highest frequency of expression in MPNST. Benign PNF with potential for malignant dedifferentiation expressed mTor, phosphorylated MEK, Sox9, and periaxin significantly higher/more frequently than other benign neurofibroma subtypes.
    CONCLUSION: In NF1-associated PNST, expression of proteins involved in Ras-signaling and development is upregulated not only in MPNST, but also in benign PNF with the potential for malignant dedifferentiation. The differences in protein expression may provide clues for understanding the therapeutic effects of substances applied for reduction of PNST in NF1.
    DOI:  https://doi.org/10.5414/NP301554
  6. Glia. 2023 May 23.
    Schwann cells as a target cell for the treatment of cancer pain.
    Wen-Jun Zhang, Chang-Lei Wu, Ji-Peng Liu.
      Tumor erosion and metastasis can invade surrounding tissues, damage nerves, and sensitize the peripheral primary receptors, inducing pain, which can potentially worsen the suffering of patients with cancer. Reception and transmission of sensory signal receptors, abnormal activation of primary sensory neurons, and activation of glial cells are involved in cancer pain. Therefore, exploring promising therapeutic methods to suppress cancer pain is of great significance. Various studies have found that the use of functionally active cells is a potentially effective way to relieve pain. Schwann cells (SCs) act as small, biologically active pumps that secrete pain-relieving neuroactive substances. Moreover, SCs can regulate the progression of tumor cells, including proliferation and metastasis, through neuro-tumor crosstalk, which emphasizes the critical role of SCs in cancer and cancer pain. The mechanisms by which SCs repair injured nerves and exert analgesia include neuroprotection, neurotrophy, nerve regeneration, neuromodulation, immunomodulation, and enhancement of the nerve-injury microenvironment. These factors may ultimately restore the damaged or stimulated nerves and contribute to pain relief. Strategies for pain treatment using cell transplantation mainly focus on analgesia and nerve repair. Although these cells are in the initial stages of nerve repair and pain, they open new avenues for the treatment of cancer pain. Therefore, this paper discusses, for the first time, the possible mechanism of SCs and cancer pain, and new strategies and potential problems in cancer pain treatment.
    Keywords:  SCs; cancer; cancer pain; nerve damage; treatment
    DOI:  https://doi.org/10.1002/glia.24391
  7. Ann Surg Oncol. 2023 May 20.
    Development and Validation of a Machine-Learning Model to Predict Early Recurrence of Intrahepatic Cholangiocarcinoma.
    Laura Alaimo, Henrique A Lima, Zorays Moazzam, Yutaka Endo, Jason Yang, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W Bauer, Sorin Alexandrescu, George A Poultsides, Shishir K Maithel, Hugo P Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Minoru Kitago, Timothy M Pawlik.
       BACKGROUND: The high incidence of early recurrence after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a detrimental effect on overall survival (OS). Machine-learning models may improve the accuracy of outcome prediction for malignancies.
    METHODS: Patients who underwent curative-intent hepatectomy for ICC were identified using an international database. Three machine-learning models were trained to predict early recurrence (< 12 months after hepatectomy) using 14 clinicopathologic characteristics. The area under the receiver operating curve (AUC) was used to assess their discrimination ability.
    RESULTS: In this study, 536 patients were randomly assigned to training (n = 376, 70.1%) and testing (n = 160, 29.9%) cohorts. Overall, 270 (50.4%) patients experienced early recurrence (training: n = 150 [50.3%] vs testing: n = 81 [50.6%]), with a median tumor burden score (TBS) of 5.6 (training: 5.8 [interquartile range {IQR}, 4.1-8.1] vs testing: 5.5 [IQR, 3.7-7.9]) and metastatic/undetermined nodes (N1/NX) in the majority of the patients (training: n = 282 [75.0%] vs testing n = 118 [73.8%]). Among the three different machine-learning algorithms, random forest (RF) demonstrated the highest discrimination in the training/testing cohorts (RF [AUC, 0.904/0.779] vs support vector machine [AUC, 0.671/0.746] vs logistic regression [AUC, 0.668/0.745]). The five most influential variables in the final model were TBS, perineural invasion, microvascular invasion, CA 19-9 lower than 200 U/mL, and N1/NX disease. The RF model successfully stratified OS relative to the risk of early recurrence.
    CONCLUSIONS: Machine-learning prediction of early recurrence after ICC resection may inform tailored counseling, treatment, and recommendations. An easy-to-use calculator based on the RF model was developed and made available online.
    Keywords:  Early recurrence; Intrahepatic cholangiocarcinoma; Machine learning; Online calculator
    DOI:  https://doi.org/10.1245/s10434-023-13636-8
  8. Front Vet Sci. 2023 ;10 1200687
    Editorial: Feline tumors of nervous system.
    Maria Teresa Mandara, Martí Pumarola.
      
    Keywords:  cat; embryonal tumor; immunophenotype; lymphoma; magnetic resonance; nervous system; schwannoma
    DOI:  https://doi.org/10.3389/fvets.2023.1200687
  9. World J Plast Surg. 2023 ;12(1): 86-89
    Schwannoma of Posterior Interosseous Nerve: A Case Report and Review of Literature.
    Navneet Sharma, Shilpi Karmakar, Lokesh Rana, Umesh Dhiman.
      Schwannomas constitute only 5% of tumors of upper limb. Schwannoma of the posterior interosseous nerve is rare. A thorough search of literature revealed only three case reports of this entity. A 33-year old female presented with insidious onset swelling over extensor aspect of right forearm for one year and deficit of extension of fourth and fifth finger for a month. Magnetic Resonance Imaging and Fine Needle Aspiration Cytology were suggestive of low- grade nerve sheath tumor. The tumor was excised under tourniquet control and magnification, using microsurgical technique. Histopathology confirmed schwannoma. Result. Patient regained her full extension of fourth and fifth finger within 1.5 months. As schwannoma does not infiltrate the nerve fibers, so a complete surgical excision is the treatment of choice. We wrote this article to draw clinicians' attention to this unusual entity. Schwannoma of PIN is a relatively rare condition. Till date, there are only three cases reported in literature. Meticulous attention to detail is required while excising large schwannomas, as there is a risk of fascicular injury during dissection. Use of magnification and microsurgical technique prevents inadvertent nerve injury.
    Keywords:  Extension; Schwannoma; Soft tissue neoplasms; Tumour
    DOI:  https://doi.org/10.52547/wjps.12.1.86
  10. J Clin Med. 2023 May 09. pii: 3356. [Epub ahead of print]12(10):
    Primary Cardiac Schwannoma: A Meta-Analysis of Individual Case Reports.
    Mohamed Rahouma, Massimo Baudo, Sherif Khairallah, Anas Dabsha, Alessandro Tafuni, Magdy M El-Sayed Ahmed, Christopher Lau, Erin Iannacone, Yoshifumi Naka, Leonard Girardi, Mario Gaudino, Roberto Lorusso, Stephanie L Mick.
      Primary cardiac schwannoma (PCS) is a neurogenic tumor that arises from Schwann cells. Malignant schwannoma (MSh) is an aggressive cancer comprising 2% of all sarcomas. Information on the proper management of these tumors is limited. Four databases were searched for case reports/series of PCS. The primary outcome was overall survival (OS). Secondary outcomes included therapeutic strategies and the corresponding outcomes. Among 439 potentially eligible studies, 53 met the inclusion criteria. The patients included had 43.72 ± 17.76 years and 28.3% were males. Over 50% of patients had MSh, with 9.4% also demonstrating metastases. Schwannoma commonly occurs in the atria (66.0%). Left-sided PCS were more common than right-sided ones. Surgery was performed in almost 90% of the cases; chemotherapy and radiotherapy were used in 16.9% and 15.1% of cases, respectively. Compared to benign cases, MSh occurs at a younger age and is commonly located on the left side. OS of the entire cohort at 1 and 3 years were 60.7%, and 54.0%, respectively. Females and males OS were similar up to 2 years follow-up. Surgery was associated with higher OS (p < 0.01). Surgery is the primary treatment option for both benign and malignant cases and was the only factor associated with a relative improvement in survival.
    Keywords:  cardiac surgery; cardiac tumors; malignant; peripheral nerve sheath tumors; schwannoma
    DOI:  https://doi.org/10.3390/jcm12103356
  11. Cureus. 2023 Apr;15(4): e38011
    Bronchial Schwannoma Incidentally Discovered via Bronchoscopy: A Case Report.
    Kyle A Burton, Matthew Karulf, Brian Pahn.
      Bronchial schwannomas are rare tumors that arise from Schwann cells and account for a very small percentage of primary lung tumors. This case report describes a rare incidental finding of a bronchial schwannoma discovered in the left lower lobe secondary carina via bronchoscopy in a 71-year-old female who presented with minimal symptoms.
    Keywords:  bronchial schwannoma; bronchoscopy; endobronchial lesion; lung tumor; spindle cells
    DOI:  https://doi.org/10.7759/cureus.38011
  12. Cureus. 2023 Apr;15(4): e38057
    Sciatica Caused by Perineural Spread of Prostate Cancer.
    Shunsuke Katsumi, Shigeru Soshi, Takayoshi Kajiwara, Mitsuru Saito.
      An 81-year-old man with a history of prostate cancer developed sciatica and underwent L4/5 laminectomy followed by L5/S1 transforaminal lumbar interbody fusion. Postoperatively, pain improved temporarily, then deteriorated. Tumor resection was performed after enhanced magnetic resonance imaging showed a mass distal to the left greater sciatic foramen. Histopathological examination showed the perineural spread of prostate cancer to the sciatic nerve. Developments in diagnostic imaging have revealed that prostate cancer can undergo perineural spread. Imaging studies are essential when sciatica is diagnosed in patients with a history of prostate cancer.
    Keywords:  degenerative lumbar disease; metastasis; perineural spread; prostate cancer; sciatic nerve; sciatica; spine surgery
    DOI:  https://doi.org/10.7759/cureus.38057
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