bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–09–15
fiveteen papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. TUMOR-INFILTRATING NOCICEPTOR NEURONS PROMOTE IMMUNOSUPPRESSION.
  2. Research trends on cancer neuroscience: a bibliometric and visualized analysis.
  3. Machine learning method based on enhanced CT to predict perineural invasion of rectal cancer.
  4. Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.
  5. Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.
  6. Targeting the peripheral neural-tumour microenvironment for cancer therapy.
  7. Gastric cancer and brain metastasis: A systematic review and meta‑analysis.
  8. Rare giant retroperitoneal melanotic schwannoma: a case report and literature review.
  9. Schwannoma of the Lower Limb: A Case Report.
  10. Application of a combined clinical prediction model based on enhanced T1-weighted image(T1WI) full volume histogram in peripheral nerve invasion (PNI) and lymphatic vessel invasion (LVI) in rectal cancer.
  11. Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.
  12. The Rare Large Common Peroneal Nerve's Schwannoma-A Case Report and Literature Review.
  13. Neurons give metastatic cells a push.
  14. Cancer-related cognitive impairment: updates to treatment, the need for more evidence, and impact on quality of life-a narrative review.
  15. Neuroma-to-Nerve Ratio: Does Size Matter?
  1. bioRxiv. 2024 Aug 26. pii: 2024.08.23.609450. [Epub ahead of print]
    TUMOR-INFILTRATING NOCICEPTOR NEURONS PROMOTE IMMUNOSUPPRESSION.
    Anthony C Restaino, Maryam Ahmadi, Amin Reza Nikpoor, Austin Walz, Mohammad Balood, Tuany Eichwald, Sebastien Talbot, Paola Drapkin Vermeer.
      Nociceptor neurons impact tumor immunity. Removing nociceptor neurons reduced myeloid-derived suppressor cell (MDSCs) tumor infiltration in mouse models of head and neck carcinoma and melanoma. Carcinoma-released small extracellular vesicles (sEVs) attract nociceptive nerves to tumors. sEV-deficient tumors fail to develop in mice lacking nociceptor neurons. Exposure of dorsal root ganglia (DRG) neurons to cancer sEVs elevated expression of Substance P, IL-6 and injury-related neuronal markers while treatment with cancer sEVs and cytotoxic CD8 T-cells induced an immunosuppressive state (increased exhaustion ligands and cytokines). Cancer patient sEVs enhanced DRG responses to capsaicin, indicating increased nociceptor sensitivity. Conditioned media from DRG and cancer cell co-cultures promoted expression of MDSC markers in primary bone marrow cells while DRG conditioned media together with cancer sEVs induced checkpoint expression on T-cells. Our findings indicate that nociceptor neurons facilitate CD8+ T cell exhaustion and enhance MDSC infiltration. Targeting nociceptor-released IL-6 emerges as a novel strategy to disrupt harmful neuro-immune interactions in cancer and enhance anti-tumor immunity.
    DOI:  https://doi.org/10.1101/2024.08.23.609450
  2. Front Neurosci. 2024 ;18 1408306
    Research trends on cancer neuroscience: a bibliometric and visualized analysis.
    Xinru Ma, Kun Deng, Yingnan Sun, Minghua Wu.
       Background: Recently, cancer neuroscience has become the focus for scientists. Interactions between the nervous system and cancer (both systemic and local) can regulate tumorigenesis, progression, treatment resistance, compromise of anti-cancer immunity, and provocation of tumor-promoting inflammation. We assessed the related research on cancer neuroscience through bibliometric analysis and explored the research status and hotspots from 2020 to 2024.
    Methods: Publications on cancer neuroscience retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and Scimago Graphica were used to analyze and visualize the result.
    Results: A total of 744 publications were retrieved, with an upward trend in the overall number of articles published over the last 5 years. As it has the highest number of publications (n = 242) and citations (average 13.63 citations per article), the United States holds an absolute voice in the field of cancer neuroscience. The most productive organizations and journals were Shanghai Jiaotong University (n = 24) and Cancers (n = 45), respectively. Monje M (H-index = 53), Hondermarck H (H-index = 42), and Amit M (H-index = 39) were the three researchers who have contributed most to the field. From a global perspective, research hotspots in cancer neuroscience comprise nerve/neuron-tumor cell interactions, crosstalk between the nervous system and other components of the tumor microenvironment (such as immune cells), as well as the impact of tumors and tumor therapies on nervous system function.
    Conclusion: The United States and European countries are dominating the field of cancer neuroscience, while developing countries such as China are growing rapidly but with limited impact. The next focal point in this field is likely to be neurotrophic factors. Cancer neuroscience is still in its infancy, which means that many of the interactions and mechanisms between the nervous system and cancer are not yet fully understood. Further investigation is necessary to probe the interactions of the nervous system with cancer cell subpopulations and other components of the tumor microenvironment.
    Keywords:  CiteSpace; VOSviewer; bibliometric analysis; cancer neuroscience; nervous system
    DOI:  https://doi.org/10.3389/fnins.2024.1408306
  3. Asian J Surg. 2024 Sep 11. pii: S1015-9584(24)02060-8. [Epub ahead of print]
    Machine learning method based on enhanced CT to predict perineural invasion of rectal cancer.
    Jiacheng Shen, Long Jin, Shengnan Yin.
      
    Keywords:  Enhanced CT imaging; Machine learning; Perineural invasion; Rectal cancer
    DOI:  https://doi.org/10.1016/j.asjsur.2024.08.258
  4. Life Sci Alliance. 2024 Dec;pii: e202302041. [Epub ahead of print]7(12):
    Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.
    Sun H Park, Shunsuke Tsuzuki, Kelly F Contino, Jenna Ollodart, Matthew R Eber, Yang Yu, Laiton R Steele, Hiroyuki Inaba, Yuko Kamata, Takahiro Kimura, Ilsa Coleman, Peter S Nelson, Enriqueta Muñoz-Islas, Juan Miguel Jiménez-Andrade, Thomas J Martin, Kimberly D Mackenzie, Jennifer R Stratton, Fang-Chi Hsu, Christopher M Peters, Yusuke Shiozawa.
      Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.
    DOI:  https://doi.org/10.26508/lsa.202302041
  5. Int J Mol Sci. 2024 Aug 27. pii: 9265. [Epub ahead of print]25(17):
    Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.
    Gun-Hoo Park, Eunkuk Park, Su-Jin Lee, Kyubin Lim, Jeonghyun Kim, Jun Eun Park, Seon-Yong Jeong.
      Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1/2 (ERK1/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-γ) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.
    Keywords:  interferon-gamma (IFN-γ); interferon-induced transmembrane protein 1 (IFITM1); malignant peripheral nerve sheet tumor (MPNST); neurofibromatosis type 1 (NF1); tumor progression
    DOI:  https://doi.org/10.3390/ijms25179265
  6. Nat Rev Drug Discov. 2024 Sep 06.
    Targeting the peripheral neural-tumour microenvironment for cancer therapy.
    Dan Yaniv, Brandi Mattson, Sebastien Talbot, Frederico O Gleber-Netto, Moran Amit.
      As the field of cancer neuroscience expands, the strategic targeting of interactions between neurons, cancer cells and other elements in the tumour microenvironment represents a potential paradigm shift in cancer treatment, comparable to the advent of our current understanding of tumour immunology. Cancer cells actively release growth factors that stimulate tumour neo-neurogenesis, and accumulating evidence indicates that tumour neo-innervation propels tumour progression, inhibits tumour-related pro-inflammatory cytokines, promotes neovascularization, facilitates metastasis and regulates immune exhaustion and evasion. In this Review, we give an up-to-date overview of the dynamics of the tumour microenvironment with an emphasis on tumour innervation by the peripheral nervous system, as well as current preclinical and clinical evidence of the benefits of targeting the nervous system in cancer, laying a scientific foundation for further clinical trials. Combining empirical data with a biomarker-driven approach to identify and hone neuronal targets implicated in cancer and its spread can pave the way for swift clinical integration.
    DOI:  https://doi.org/10.1038/s41573-024-01017-z
  7. Mol Clin Oncol. 2024 Nov;21(5): 77
    Gastric cancer and brain metastasis: A systematic review and meta‑analysis.
    George Fotakopoulos, Grigorios Christodoulidis, Vasiliki Epameinondas Georgakopoulou, Nikolaos Trakas, Pagona Skapani, Konstantinos Panagiotopoulos, Demetrios A Spandidos, Nicolas Foroglou.
      Gastric cancer (GC) constitutes one of the most wide-ranging cancers, with brain metastasis (BM) being a markedly uncommon and unfavorable outcome. The present meta-analysis evaluated the relationship between no-surgical treatment vs. additional surgical BM resection on the patient's quality of life and potential survival using electronic databases, including PubMed (1980-April 2024), Medline (1980-April 2024), Cochrane Library, and EMBASE (1980-April 2024). After a literature search, six articles were included in the final study pool. The number of patients with BM and conservative treatment was 289 (80.05%) compared with those that underwent an additional surgical resection 72 (19.95%). The mean age was 59.2 years, and the males were 195 (73.8%) of 264 available from five studies. The findings of the present meta-analysis revealed that the curative effect of BM tumor resection on patients with GC undergoing additional treatment with stereotactic radiosurgery, whole-brain radiotherapy or chemotherapy was favorable for their survival.
    Keywords:  brain metastasis; conservative or no-surgical treatment; gastric cancer; surgical resection; survival outcomes
    DOI:  https://doi.org/10.3892/mco.2024.2775
  8. Front Oncol. 2024 ;14 1448112
    Rare giant retroperitoneal melanotic schwannoma: a case report and literature review.
    Pan Chen, Junfeng Cheng, Lin Zhang.
       Background: Melanotic schwannoma (MS), a rare variant of peripheral nerve sheath tumor, is especially infrequent when originating from the peritoneum. Its definitive diagnosis relies on postoperative histopathological examination and immunohistochemical analysis, while preoperative diagnosis is difficult.
    Case presentation: In the present study, we reported a rare case of giant MS in the retroperitoneum, which was previously misdiagnosed before surgery. However, intraoperative exploration revealed it was retroperitoneal tumor. The tumor had invaded the abdominal aorta and bilateral common illiac artery walls. A surgical resection was subsequently executed, and postoperative histopathological examination confirmed it as a MS.
    Conclusion: The incidence of peritoneal MS is extremely rare, and surgical resection remains the preferred treatment modality. Given the absence of established guidelines for postoperative adjuvant therapy, long-term follow-up becomes imperative to accumulate valuable clinical expertise.
    Keywords:  malignant melanotic nerve sheath tumor(MMNST); melanotic schwannoma(MS); rare giant tumor; retroperitoneal schwannoma; surgical resection
    DOI:  https://doi.org/10.3389/fonc.2024.1448112
  9. Cureus. 2024 Aug;16(8): e66616
    Schwannoma of the Lower Limb: A Case Report.
    Nikolozi Kutalia, Magda Bolkvadze, Mehmet N Erdem.
      Schwannoma is a benign tumor of the peripheral nerve sheath and is a unique clinical entity when localized to a lower limb. Growing as a painless nodule, it might be misdiagnosed by many medical professionals as another benign soft tissue skin condition, such as lipoma, myxoma, or ganglion cyst. Definitive diagnosis of peripheral schwannoma is made by biopsy and histopathologic evaluation, followed by surgical excision, which is the definitive treatment of the tumor. Classic symptoms of schwannoma of the lower limb are peripheral neuropathy (tingling, burning sensations) and motor impairment (weakness, paralysis of the affected limb). MRI imaging and biopsy are the most useful diagnostic methods for peripheral schwannoma, followed by surgical excision, which is the treatment of choice. Postoperative complications, if present, are minimal and rare. Because of the slow-growing nature of the tumor and the complexity of the lower limb's nervous and structural network, it is often asymptomatic and is challenging to diagnose at a primary stage. That is why we want to spread awareness and draw the reader's attention to this rare case of a patient with schwannoma on the left lower limb.
    Keywords:  antoni a and antoni b areas; benign peripheral nerve sheath tumor; cerebellopontine angle tumours; painless nodule; peripheral schwannoma
    DOI:  https://doi.org/10.7759/cureus.66616
  10. Abdom Radiol (NY). 2024 Sep 10.
    Application of a combined clinical prediction model based on enhanced T1-weighted image(T1WI) full volume histogram in peripheral nerve invasion (PNI) and lymphatic vessel invasion (LVI) in rectal cancer.
    Yumeng Zhang, Huaqing Tan, Bin Huang, Xinjian Guo, Yuntai Cao.
       PURPOSE: This study aims to use a combined clinical prediction model based on enhanced T1-weighted image(T1WI) full volume histogram to predict preoperative peripheral nerve invasion (PNI) and lymphatic vessel invasion (LVI) in rectal cancer.
    METHODS: We included a total of 68 PNI patients and 80 LVI patients who underwent surgical resection and pathological confirmation of rectal cancer. According to the PNI/LVI status, patients were divided into PNI positive group (n = 39), the PNI negative group (n = 29), LVI positive group (n = 48), and the LVI negative group (n = 32). External validation included a total of 42 patients with nerve and vascular invasion in patients with surgically resected and pathologically confirmed rectal cancer at another healthcare facility, with a PNI positive group (n = 32) and a PNI-negative group (n = 10) as well as an LVI positive group (n = 35) and LVI-negative group (n = 7). All patients underwent 3.0T magnetic resonance T1WI enhanced scanning. We use Firevoxel software to delineate the region of interest (ROI), extract histogram parameters, and perform univariate analysis, LASSO regression, and multivariate logistic regression analysis in sequence to screen for the best predictive factors. Then, we constructed a clinical prediction model and plotted it into a column chart for personalized prediction. Finally, we evaluate the performance and clinical practicality of the model based on the area under curve (AUC), calibration curve, and decision curve.
    RESULTS: Multivariate logistic regression analysis found that variance and the 75th percentile were independent risk factors for PNI, while maximum and variance were independent risk factors for LVI. The clinical prediction model constructed based on the above factors has an AUC of 0.734 (95% CI: 0.591-0.878) for PNI in the training set and 0.731 (95% CI: 0.509-0.952) in the validation set; The training set AUC of LVI is 0.701 (95% CI: 0.561-0.841), and the validation set AUC is 0.685 (95% CI: 0.439-0.932). External validation showed an AUC of 0.722 (95% CI: 0.565-0.878) for PNI; and an AUC of 0.706 (95% CI: 0.481-0.931) for LVI.
    CONCLUSIONS: This study indicates that the combination of enhanced T1WI full volume histogram and clinical prediction model can be used to predict the perineural and lymphovascular invasion status of rectal cancer before surgery, providing valuable reference information for clinical diagnosis.
    Keywords:  Clinical features; Clinical prediction model; Histogram; Lymphatic vessel invasion; Peripheral nerve invasion; Rectal cancer
    DOI:  https://doi.org/10.1007/s00261-024-04556-6
  11. Cancer Lett. 2024 Sep 05. pii: S0304-3835(24)00608-6. [Epub ahead of print]603 217213
    Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.
    Rong Hua, Hong-Fei Yao, Zi-Yu Song, Feng Yu, Zhao-Yu Che, Xiao-Fang Gao, Yan-Miao Huo, Wei Liu, Yong-Wei Sun, Min-Wei Yang, Jian-Yu Yang, Shan Zhang, Jun-Feng Zhang.
      Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of 'two points of intraneural (endoneural) invasion in the case of four pathological slides' has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.
    Keywords:  Endoneural invasion; Intraneural invasion; Nerve invasion; Pancreatic ductal adenocarcinoma; Perineural invasion
    DOI:  https://doi.org/10.1016/j.canlet.2024.217213
  12. Case Rep Oncol Med. 2024 ;2024 9397436
    The Rare Large Common Peroneal Nerve's Schwannoma-A Case Report and Literature Review.
    Rudiansyah Harahap, Nurmaliannysa Dwinandia Harahap.
      Schwannoma in the popliteal fossa is still rare, often diagnosed late because it grows slowly and has no symptoms. It is often misdiagnosed with connective tissue tumors or with neurological disorders originating in the spine or disorders of the peroneal nerve. Schwannoma within the common peroneal nerve is still rare in the popliteal fossa, with most tumor sizes around 2 cm in diameter due to their smaller size of nerve but can cause neurologic disturbance, especially when it is large. And over a long time, it can cause serious complaints like neurological deficits and make surgery difficult by leaving greater sequelae. There is no data yet showing the incidence of schwannoma in the common peroneal nerve. In this case, a 36-year-old woman, for 5 years, feels soreness in the popliteal fossa and pain in the right instep, suspected that a nerve was pinched, due to an abnormality in the spine. As time went on, there was a lump in the fold of the right knee, suspected to be a Baker's cyst. As time went by, the complaint was burning pain in the right instep to the lateral ankle and distal right lower leg, disturbing sleep. Tinel's sign was positive. The right instep has hypoesthesia and a slight drop in the foot. On radiological examination of the right knee, a circumferential mass appeared, measuring 5 cm × 4 cm. The diagnosis is suspicious for a common peroneal nerve tumor. The encapsulated operation to remove the tumor was carried out with a size measuring 5 cm × 4.5 cm × 4 cm. The histopathological examination showed schwannoma. After surgery, the pain disappeared, hypoesthesia and a slight drop in the foot underwent physiotherapy, and stimulation with the result gradually improved. A thorough early examination includes correct and systematic anamnesis, physical examination, and neurological evaluation such as paraesthesia, hypoesthesia, and Tinel's sign; also, additional examinations, such as radiographic, ultrasound, and MRI, are needed for early detection of schwannoma so that delays in diagnosis and surgery can be avoided to prevent neurological deficits.
    Keywords:  common peroneal nerve; neurological deficit; schwannoma
    DOI:  https://doi.org/10.1155/2024/9397436
  13. Nat Rev Drug Discov. 2024 Sep 09.
    Neurons give metastatic cells a push.
    M Teresa Villanueva.
      
    Keywords:  Cancer; Drug discovery; Neuroscience
    DOI:  https://doi.org/10.1038/d41573-024-00144-x
  14. Ann Palliat Med. 2024 Sep 09. pii: apm-24-70. [Epub ahead of print]
    Cancer-related cognitive impairment: updates to treatment, the need for more evidence, and impact on quality of life-a narrative review.
    Yesol Yang, Diane Von Ah.
       BACKGROUND AND OBJECTIVE: Due to advances in early detection and treatment options, non-central nervous system (non-CNS) cancer survivors are living longer, even those with metastatic disease. Many of these survivors will experience enduring symptoms of breast cancer, such as cancer-related cognitive impairment (CRCI). Although CRCI is bothersome and, in some cases, potentially debilitating, little research has been done to address this symptom. Thus, the overarching goal of this narrative review is to provide both an overview of the problem of CRCI and its impact and focus on the latest research aimed at addressing CRCI in non-CNS cancer survivors.
    METHODS: A MEDLINE database (PubMed) search was conducted for terms related to non-CNS cancer, cognition, impacts of CRCI, and interventions. The English-language articles published until April 8th, 2024, were included in the search.
    KEY CONTENT AND FINDINGS: CRCI includes self-reported cognitive complaints and/or impaired performance in multiple cognitive domains, including memory, processing speed, attention, and executive function. CRCI, in turn, can have a significant impact on everyday functioning, work ability, work engagement and productivity, and overall quality of life (QoL) of cancer survivors. While some researchers have examined pharmacological approaches, the vast majority of the interventional studies to date to address CRCI has focused on non-pharmacological approaches. Three of the most common non-pharmacological approaches are physical activity or exercise, mind-body approaches [e.g., mindfulness-based stress reduction (MBSR)], and cognitive rehabilitative approaches [e.g., cognitive training (CT) and cognitive behavioral therapy (CBT)].
    CONCLUSIONS: Addressing the cognitive health of cancer survivors is imperative but has only recently been the focus of interventional research. More research in larger and more diverse samples of non-CNS cancer survivors is needed to identify effective ways to manage CRCI for all cancer survivors. Overall, maintaining cognitive health, especially in cancer survivors who are at increased risk for deficits, is a national health care priority that should not be ignored.
    Keywords:  Cancer-related cognitive impairment (CRCI); management of cognitive impairment; non-central nervous system cancer survivors (non-CNS cancer survivors)
    DOI:  https://doi.org/10.21037/apm-24-70
  15. Neurosurgery. 2024 Sep 09.
    Neuroma-to-Nerve Ratio: Does Size Matter?
    Daniel T Weigel, Floris V Raasveld, Wen-Chih Liu, Maximilian Mayrhofer-Schmid, Charles D Hwang, Vlad Tereshenko, William Renthal, Clifford J Woolf, Ian L Valerio, Kyle R Eberlin.
       BACKGROUND AND OBJECTIVES: Anatomic features of neuromas have been explored in imaging studies. However, there has been limited research into these features using resected, ex vivo human neuroma specimens. The aim of this study was to investigate the influence that time may have on neuroma growth and size, and the clinical significance of these parameters.
    METHODS: Patients who underwent neuroma excision between 2022 through 2023 were prospectively included in this study. Neuroma specimens were obtained after operative resection. Standardized neuroma size measurements, expressed as a neuroma-to-nerve ratio (NNR), were conducted with ImageJ software. Pain data (numeric rating scale, 0-10) were prospectively recorded during preoperative evaluation, and patient factors were collected from chart reviews.
    RESULTS: Fifty terminal neuroma specimens from 31 patients were included, with 94.0% of the neuromas obtained from individuals with amputations. Most neuromas were excised from the lower extremities (n = 44, 88.0%). The neuromas had a median NNR of 2.45, and the median injury to neuroma excision interval was 6.3 years. Larger NNRs were associated with a longer injury to neuroma excision interval and with a smaller native nerve diameter. In addition, sensory nerves were associated with a larger NNR compared with mixed nerves. NNR was not associated with preoperative pain or with anatomical nerve distribution.
    CONCLUSION: This study suggests that neuromas seem to continue to grow over time and that smaller nerves may form relatively larger neuromas. In addition, sensory nerves develop relatively larger neuromas compared with mixed nerves. Neuroma size does not appear to correlate with pain severity. These findings may stimulate future research efforts and contribute to a better understanding of symptomatic neuroma development.
    DOI:  https://doi.org/10.1227/neu.0000000000003166
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