bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–08–11
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories



  1. Nature. 2024 Aug 07.
      
    Keywords:  Brain; Cancer; Medical research; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-024-02555-7
  2. Nature. 2024 Aug 07.
      Tumour innervation is associated with worse patient outcomes in multiple cancers1,2, which suggests that it may regulate metastasis. Here we observed that highly metastatic mouse mammary tumours acquired more innervation than did less-metastatic tumours. This enhanced innervation was driven by expression of the axon-guidance molecule SLIT2 in tumour vasculature. Breast cancer cells induced spontaneous calcium activity in sensory neurons and elicited release of the neuropeptide substance P (SP). Using three-dimensional co-cultures and in vivo models, we found that neuronal SP promoted breast tumour growth, invasion and metastasis. Moreover, patient tumours with elevated SP exhibited enhanced lymph node metastatic spread. SP acted on tumoral tachykinin receptors (TACR1) to drive death of a small population of TACR1high cancer cells. Single-stranded RNAs (ssRNAs) released from dying cells acted on neighbouring tumoural Toll-like receptor 7 (TLR7) to non-canonically activate a prometastatic gene expression program. This SP- and ssRNA-induced Tlr7 gene expression signature was associated with reduced breast cancer survival outcomes. Therapeutic targeting of this neuro-cancer axis with the TACR1 antagonist aprepitant, an approved anti-nausea drug, suppressed breast cancer growth and metastasis in multiple models. Our findings reveal that tumour-induced hyperactivation of sensory neurons regulates multiple aspects of metastatic progression in breast cancer through a therapeutically targetable neuropeptide/extracellular ssRNA sensing axis.
    DOI:  https://doi.org/10.1038/s41586-024-07767-5
  3. Front Oncol. 2024 ;14 1421067
      Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor with a high metastatic potential. Perineural invasion (PNI) occurs in the early stages of PDAC with a high incidence rate and is directly associated with a poor prognosis. It involves close interaction among PDAC cells, nerves and the tumor microenvironment. In this review, we detailed discuss PNI-related pain, six specific steps of PNI, and treatment of PDAC with PNI and emphasize the importance of novel technologies for further investigation.
    Keywords:  neural reprogramming; pain; pancreatic ductal adenocarcinoma; perineural invasion; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2024.1421067
  4. Surg Case Rep. 2024 Aug 07. 10(1): 183
       BACKGROUND: Appendiceal goblet cell adenocarcinoma (GCA) is a rare subtype of primary appendiceal adenocarcinoma with an incidence of 1-5 per 10,000,000 people per year. Appendiceal tumors are often diagnosed after appendectomy for acute appendicitis. Notably, however, there is currently no standard treatment strategy for GCA, including additional resection. We report a case of appendiceal GCA with perineural extension into the cecum, in which ileal resection was considered effective.
    CASE PRESENTATION: A 41-year-old man was diagnosed with acute appendicitis and underwent appendectomy. Histopathological findings revealed GCA (T3, Pn1). He was referred to our hospital for additional resection. Preoperative examination indicated a diagnosis of GCA cT3N0M0. Laparoscopic ileocecal resection and D3 lymph node dissection were performed 2 months after initial appendectomy. The patient had a good postoperative course and was discharged 8 days after surgery. Histopathological findings showed a GCA invading the cecum, despite an intact appendiceal stump, no lymph node metastasis, no vascular invasion, and no horizontal extension into the submucosa. Direct invasion of the tumor through the serosa was not observed, but perineural extension was conspicuous in the cecum, suggesting that the GCA extended into the cecum via perineural invasion. The resection margins were negative. The patient has survived free of recurrence for a year after ileocecal resection.
    CONCLUSIONS: The current patient was diagnosed with appendiceal GCA following appendectomy for acute appendicitis. Despite intact of appendiceal stump and no evidence of lymph node or distant metastasis, he underwent laparoscopic ileocecal resection and D3 lymph node dissection 2 months after initial appendectomy, with a favorable outcome. Despite the detection of perineural invasion, the patient declined adjuvant therapy. This case suggests that extensive resection may be required in patients with appendiceal GCA, but the role of adjuvant therapy remains unclear.
    Keywords:  Appendix; Goblet cell adenocarcinoma; Perineural extension
    DOI:  https://doi.org/10.1186/s40792-024-01984-w
  5. Ann Med Surg (Lond). 2024 Aug;86(8): 4921-4926
       Introduction and importance: Schwannomas are benign tumors that arise from Schwann cells commonly located in peripheral nerves. Depending on the size and location of sciatic nerve Schwannoma clinical manifestations can either varies from symptoms simulating radiculopathies such as positive Lasegue sign on the affected side, gait weakness and paresthesia or just present with pain and an associated palpable mass.
    Case presentation: The authors present a case of a 34-year-old female patient suffering from pain, gait weakness, and a palpable mass since many months. The palpable mass was present in the posterior region of the left lower limb. Imaging studies reveal an extensive lesion measuring 35 cm×8 cm that extends from the gluteal region to the left popliteal fossa.
    Clinical discussion: The finding of a palpable mass during physical examination guided us towards the diagnostic suspicion and thus necessitating the direct imaging studies. When approaching such type of patients, a history of neurofibromatosis must be ruled out due to its frequent association. Surgical resection should focus on the preservation of neurovascular structures, which offers improvement of the symptoms and the quality of life of patients.
    Conclusion: Giant sciatic nerve schwannoma if excised completely can lead to relieve of symptoms. Although recurrences are uncommon follow-up for years is necessary.
    Keywords:  neurilemmoma; plexiform schwannomatosis; sciatic nerve
    DOI:  https://doi.org/10.1097/MS9.0000000000002331
  6. Curr Treat Options Oncol. 2024 Aug 05.
       OPINION STATEMENT: Cutaneous squamous cell carcinoma (cSCC) stands as the second most prevalent non-melanoma skin cancer worldwide, comprising approximately 20% of all cutaneous malignancies. Determining its precise incidence poses challenges; however, reports indicate a global increase in its prevalence. At the time of diagnosis, the majority of cSCCs are localized, resulting in favorable 5-year cure rates surpassing 90%. Nevertheless, a subset of patients (3-7%) encounters locally advanced or metastatic cSCC, leading to substantial morbidity and mortality. The risk of metastasis ranges from 0.1% to 9.9%, carrying an associated mortality risk of 2.8%. Factors influencing recurrence, metastasis, and disease-specific mortality underscore the significance of perineural invasion (PNI) as a key indicator. Patients with PNI may manifest clinical symptoms and/or radiologic signs of PNI, while the majority remain asymptomatic, and PNI is frequently identified upon histologic examination. Despite its lower frequency compared to other cancer types, PNI serves as a recognized adverse prognostic factor for cSCC. Surgery is the elective treatment for these patients, while the role of adjuvant radiotherapy (ART) is yet contentious and have not been conclusively assessed, particularly in clear surgical margin. Prospective comparative studies are required to comprehensively evaluate the benefit and the risks of ART for cSCC and PNI patients.
    Keywords:  Adjuvant therapy; Cutaneous squamous cell carcinoma; Perineural invasion; Surgery
    DOI:  https://doi.org/10.1007/s11864-024-01234-z
  7. Semin Neurol. 2024 Aug 05.
      Patients with cancer experience high rates of alterations in mental status. The mechanisms for altered mental status (AMS) in this population are manifold. The cancer itself may cause AMS through direct invasion of the central nervous system or as metastatic leptomeningeal spread. However, cancer patients are also vulnerable to tumor-associated complications such as seizures, cerebral edema, strokes, or cancer treatment-related complications such as infections, direct neural injury from radiation or chemotherapy, edema, or dysregulated autoimmune response from immunotherapies. Both during treatment and as sequelae, patients may suffer neurocognitive complications from chemotherapy and radiation, medications or opportunistic infections, as well as toxic-metabolic, nutritional, and endocrine complications. In this review, we describe a clinical approach to the cancer patient presenting with AMS and discuss the differential drivers of AMS in this patient population. While common etiologies of AMS in noncancer patients (toxic-metabolic or infectious encephalopathy, delirium) are also applicable to cancer patients, we additionally provide a cancer-specific differential diagnosis that warrants special consideration in the cancer patient with AMS.
    DOI:  https://doi.org/10.1055/s-0044-1788806
  8. Cancer Nurs. 2024 Aug 01.
       BACKGROUND: Individuals who undergo chemotherapy for cancer are at elevated risk of developing depressive symptoms, yet substantial interindividual variation exists in trajectories of these symptoms.
    OBJECTIVE: To examine interindividual variations in trajectories of depressive symptoms during 2 cycles of chemotherapy and to evaluate associations between demographic and clinical characteristics, symptom severity scores, psychological adjustment characteristics (eg, stress and coping), and initial levels and trajectories of depressive symptoms.
    METHODS: Patients (n = 1323) diagnosed with breast, gynecologic, lung, or gastrointestinal cancer completed the Center for Epidemiological Studies-Depression Scale 6 times, over 2 cycles of chemotherapy. At enrollment, patients provided demographic information and completed a broad range of symptom, stress, and coping measures. Hierarchical linear modeling was used to identify characteristics associated with initial levels and trajectories of depressive symptoms.
    RESULTS: Interindividual differences in initial levels of depressive symptoms were associated with marital status, functional status, level of comorbidity, chemotherapy toxicity, sleep disturbance, morning fatigue, cognitive function, global and cancer-related stress, and coping characteristics (ie, sense of coherence, venting, behavioral disengagement, and self-blame). Interindividual differences in depression trajectories were associated with education, cancer type, chemotherapy toxicity, sleep disturbance, evening energy, evening fatigue, cognitive function, global and cancer-related stress, and self-blame.
    CONCLUSIONS: We present new findings concerning the trajectories and predictors of depressive symptoms during chemotherapy.
    IMPLICATIONS FOR PRACTICE: Modifiable risk factors (eg, stress and coping) are important targets for intervening to address depressive symptoms in oncology patients.
    DOI:  https://doi.org/10.1097/NCC.0000000000001380
  9. Heliyon. 2024 Jul 30. 10(14): e34522
       Objective: Intrathecal drug delivery systems (IDDS) have been clinically applied to treat refractory cancer-related pain for years. In this study, we demonstrate the current clinical practice and outcomes of IDDS for cancer pain management over a 3-year period at a single tertiary medical center in China.
    Methods: Patients who received IDDS implantation for cancer-related pain from 2021 to 2023 were identified. The electronic medical records of all eligible patients were retrospectively reviewed for study data including baseline characteristics, IDDS variables and postoperative clinical outcomes.
    Results: A total of 96 consecutive individuals were identified for analysis and complete follow-up information was available in 72 patients with a follow-up rate of 75 %. Patients were 49.0 % female with a mean age of 62 ± 10 years. The top five cancer types in IDDS population were lung (34.4 %), colorectal (17.7 %), pancreatic (11.5 %), breast (5.2 %) and liver (4.2 %) cancer. The median duration from cancer diagnosis to IDDS implantation was 24 months (interquartile range [IQR] 12-48 months) and from pain onset to IDDS implantation was 6 months (IQR 2-12 months). In addition, the median oral morphine equivalents (OME) daily dose was 290 mg (IQR 100-632 mg). Mean NRS was 7.5 ± 0.8 before implantation and decreased to an average of 3.0 ± 1.1 after IDDS (p < 0.001). Median overall survival after IDDS implantation was 3 months (IQR 2-6 months). Overall, 75 % family members of cancer patients were satisfied with IDDS in relieving cancer pain.
    Conclusion: IDDS therapy is a valuable option for patients suffering from cancer pain. More and more cancer pain patients receive IDDS to treat pain during the 3-year study period.
    Keywords:  Analgesia; Cancer pain; Intrathecal drug delivery systems; Intrathecal pump; Pain management; Retrospective study
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e34522
  10. Curr Treat Options Oncol. 2024 Aug 05.
       OPINION STATEMENT: Neuropathic cancer pain is experienced by 30-40% of patients with cancer. It significantly reduces quality of life and overall wellbeing for patients living with and beyond cancer. The underlying mechanisms of neuropathic pain in patients with cancer are complex and involve direct tumour involvement, nerve compression or infiltration, chemotherapy and/or radiotherapy-induced nerve damage, or post-surgical complications. It is crucial for healthcare professionals to assess and manage neuropathic cancer pain effectively. There is increasing recognition that standardisation of neuropathic pain assessment leads to tailored management and improved patient outcomes. Pain management strategies, including medication, interventional analgesia, physical and complementary therapy, can help alleviate neuropathic pain and improve the patient's comfort and quality of life.
    Keywords:  Chronic pain; Guidelines; Management; Neuropathic cancer pain; Treatment
    DOI:  https://doi.org/10.1007/s11864-024-01248-7