bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022‒04‒03
eleven papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

  1. Pathol Int. 2022 Mar 30.
      Perineural invasion (PNI) at Auerbach's plexus in colorectal cancer (CRC), known as intramural PNI, is associated with adverse prognostic outcomes. This study aimed to characterize the three-dimensional (3D) architecture of CRC with intramural PNI and to evaluate the morphological features of tumor invasion around nerve tissue. Serial tissue sections from two cases of CRC were stained with cytokeratin AE1/AE3 and an anti-S-100 protein antibody. 3D models were reconstructed by scanning the virtual slides. In one case, intramural PNI was observed at the horizontal invasive front. The 3D reconstruction model showed tumor cells that appeared to infiltrate along the nervous meshwork, the structure of which was preserved. In the other case, intramural PNI was observed both at and behind the horizontal invasive front, and the 3D reconstruction model showed that the tumor cells appeared to be involved with nerve cells at the focal part of the horizontal invasive front. However, the nervous meshwork structure was not well identified in cancer-involved areas. This is the first study to characterize the 3D structure of tumor invasion around nerve tissue in CRC, demonstrating the morphological features of intramural PNI in CRC.
    Keywords:  3D reconstruction; colorectal cancer; intramural perineural invasion
  2. Front Oncol. 2022 ;12 855615
      Background & Objective: Perineural invasion is an important biological feature of hilar cholangiocarcinoma (HCCA). We developed a whole-mount histologic large sections (WHLS) of the liver to evaluate peripheral nerve invasion (PNI) of HCCA.Methods: Using sampling, fixation, dehydration, embedding, sectioning, hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, and scanning, the characteristics of intrahepatic and extrahepatic PNI in 20 patients with Bismuth type III and type IV HCCA were analyzed with WHLS. Correlation between the characteristics of nerve invasion and tumor size, vascular invasion (artery, portal vein), degree of differentiation, microvascular invasion (MVI), carbohydrate antigen19-9 (CA19-9), and differentiation degree of HCCA was statistically evaluated.
    Results: The WHLS of the liver was successfully established, which enabled us to observe intrahepatic and extrahepatic distribution of HCCA and whether surrounding tissues including nervous, blood, and lymph vessels were infiltrated. Extrahepatic and intrahepatic PNI were identified in 20 (100%) patients and 1 (5.0%) patient, respectively. Vessel density decreased in most invaded nerves presented by CD-34, which correlated with 100% of poorly differentiated and 83% of moderately differentiated tumors (P<0.008).
    Conclusion: This study established a WHLS of the liver that can be used for clinical diagnosis and research, and confirmed that extrahepatic PNI is prevalent, but intrahepatic nerve invasion is rare and does not accompany the invasion scope of bile ducts in types III and IV HCCA. In addition, moderately and poorly differentiated malignant tumors are more prone to PNI, independent of blood supply.
    Keywords:  panoramic immunohistochemistry; pathological digital imaging; pathological methodology; tumor biological behavior; whole-mount histologic large sections
  3. BMJ Case Rep. 2022 Mar 30. pii: e248597. [Epub ahead of print]15(3):
      Primary lymphoma of the peripheral nerve is very rare and occurs most frequently in sciatic nerves. We describe the first patient reported in literature with a primary lymphoma in a pure sensory peripheral nerve of the upper limb. A woman in her 40s, with painful swelling and dysaesthesias in her left forearm in the past 3 months, was presented at our unit. Clinical MRI and ultrasound findings revealed a lesion that showed signs of a peripheral nerve sheath tumour. After complete excision, morpho-pathological evaluation revealed a primary B-cell lymphoma. The patient underwent radiotherapy and at the last follow-up there were no signs of residual pathology. Peripheral neuropathy may be caused by a lymphoma involving the nerve. Hand surgeons have to distinguish primary lymphoma of the peripheral nerves from schwannoma for their different clinical behaviour.
    Keywords:  Cancer intervention; Neurooncology; Orthopaedics
  4. Surg Oncol. 2022 Mar 24. pii: S0960-7404(22)00042-1. [Epub ahead of print]41 101749
      BACKGROUND: The diagnostic accuracy of computed tomography (CT) for colon cancer is low, and the preoperative risk factors for locally advanced colon cancer are unknown. This study aimed to evaluate the correlation between preoperative CT scan findings and oncologic outcomes and to identify risk factors associated with locally advanced colon cancer.MATERIALS AND METHODS: Patients diagnosed with clinical stage (cT) 4 colon cancer based on preoperative CT scan findings who underwent curative surgery between January 2005 and December 2015 were retrospectively studied. Patients were divided according to pathologic stage (pT) into pT3 (n = 114) and pT4 (n = 102).
    RESULTS: The disease-free survival rate was significantly different between the pT3 and pT4 groups (88.6% vs. 68.6%, p < 0.001). The overall survival rate of the pT3 group was significantly higher than that of the pT4 group (91.2% vs. 76.5%, p = 0.002). Perineural invasion and tumor budding were identified as preoperative risk factors predisposing to pT4 staging (p = 0.044, p = 0.001).
    CONCLUSION: The survival rate of pT3 patients was significantly higher than that of pT4 patients with a preoperative cT4 diagnosis. This suggests that when planning for neoadjuvant chemotherapy in locally advanced colon cancer, preoperative CT scan findings may overestimate clinical staging and lead to inappropriate treatment. Thus, there is a need for a new modality to evaluate local advancement in colon cancer.
    Keywords:  Clinical stage; Colon cancer; Diagnosis; Neoadjuvant therapy; Survival
  5. Front Oncol. 2022 ;12 802210
      Cancer is a leading cause of death, and surgery is an important treatment modality. Laboratory research and retrospective studies have raised the suspicion that the choice of anesthetics for cancer surgery might affect the course of cancerous disease. The aim of this review is to provide a critical overview of the current state of knowledge. Inhalational anesthesia with volatiles or total intravenous anesthesia (TIVA) with propofol are the two most commonly used anesthetic techniques. Most data comparing volatile anesthetics with TIVA is from either in vitro or retrospective studies. Although conflicting, data shows a trend towards favoring propofol. Opioids are commonly used in anesthesia. Data on potential effects of opioids on growth and recurrence of cancer are scarce and conflicting. Preclinical studies have shown that opioids stimulate cancer growth through the µ-opioid receptor. Opioids also act as immunosuppressants and, therefore, have the potential to facilitate metastatic spread. However, the finding of an adverse effect of opioids on tumor growth and cancer recurrence by some retrospective studies has not been confirmed by prospective studies. Regional anesthesia has not been found to have a beneficial effect on the outcome of surgically treated cancer patients, but prospective studies are scarce. Local anesthetics might have a beneficial effect, as observed in animal and in vitro studies. However, prospective clinical studies strongly question such an effect. Blood products, which may be needed during extensive cancer surgery suppress the immune system, and data strongly suggest a negative impact on cancer recurrence. The potential effects of other commonly used anesthetic agents on the outcome of cancer patients have not been sufficiently studied for drawing valid conclusions. In conclusion, laboratory data and most retrospective studies suggest a potential advantage of TIVA over inhalational anesthesia on the outcome of surgical cancer patients, but prospective, randomized studies are missing. Given the state of weak scientific evidence, TIVA may be used as the preferred type of anesthesia unless there is an individual contraindication against it. Studies on the effects of other drugs frequently used in anesthesia are limited in number and quality, and have found conflicting results.
    Keywords:  anesthesia; cancer; cancer recurrence; propofol; volatile anesthesia
  6. Annu Rev Neurosci. 2022 Apr 01.
      Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interaction occurs at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interaction. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see for revised estimates.
  7. Nat Biomed Eng. 2022 Mar 31.
      Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals' sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators.
  8. Ann Med Surg (Lond). 2022 Apr;76 103475
      Vagus nerve schwannoma is a very rare benign nerve tumor. Pheochromocytoma is a rare, mostly benign tumor of the adrenal medulla with a large clinical spectrum. Their association is uncommon. The management of both tumors depends solely on surgery. The surgery of vagal schwannomas is particularly challenging considering the anatomical compositions of the area. Here, we report a case of a 76 year-old patient with cervical vagal schwannoma and benign pheochromocytoma association. We discuss the diagnosis and the surgical management of these tumors.
    Keywords:  Immunohistichimical staining; Pheochromocytoma; Resection; Schwannoma; Vagus nerve
  9. eNeuro. 2022 Mar 31. pii: ENEURO.0026-22.2022. [Epub ahead of print]
      The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g. cough, bronchospasm). Airway innervation is heterogeneous, and distinct afferent subsets have distinct functional responses. However, little is known of the innervation patterns of subsets within the lung. A neuroanatomical map is critical for understanding afferent activation under physiological and pathophysiological conditions. Here, we quantified the innervation of the mouse lung by vagal and dorsal root ganglion (DRG) sensory subsets defined by the expression of Pirt (all afferents), 5HT3 (vagal nodose afferents), Tac1 (tachykinergic afferents) and TRPV1 (defensive/nociceptive afferents) using Cre-mediated reporter expression. We found that vagal afferents innervate almost all conducting airways and project into the alveolar region, whereas DRG afferents only innervate large airways. Of the two vagal ganglia, only nodose afferents project into the alveolar region, but both nodose and jugular afferents innervate conducting airways throughout the lung. Many afferents that project into the alveolar region express TRPV1. Few DRG afferents expressed TRPV1. ∼25% of blood vessels were innervated by vagal afferents (many were Tac1+). ∼10% of blood vessels had DRG afferents (some were Tac1+), but this was restricted to large vessels. Lastly, innervation of neuroepithelial bodies correlated with the cell number within the bodies. In conclusion, functionally distinct sensory subsets have distinct innervation patterns within the conducting airways, alveoli and blood vessels. Physiological (e.g. stretch) and pathophysiological (e.g. inflammation, edema) stimuli likely vary throughout these regions. Our data provide a neuroanatomical basis for understanding afferent responses in vivo.Significance StatementActivation of airway sensory afferent nerves by physical and chemical stimuli evokes reflex changes in respiratory function. Multiple afferent subsets exist, including those activated by noxious stimuli (so-called "nociceptors"), which have distinct functions. The inappropriate activation of airway afferents, especially nociceptors, in inflammatory/infectious disease contributes to morbidity (e.g. bronchospasm, mucus secretion, cough). Despite extensive electrophysiological characterization of airway afferent subsets, little is known of their innervation patterns. To date, afferent subsets have been qualitatively identified in airway tissue, mostly using immunohistochemistry (which often lacks specificity and signal strength). Here, we have used Cre-dependent reporter expression to quantify genetically-defined afferent subsets. Thus, we provide a neuroanatomical map of the sensory innervation of conducting airways, alveoli and blood vessels throughout the lung.
    Keywords:  DRG; lung; mapping; nociceptor; sensory nerve; vagal ganglia
  10. Methods Mol Biol. 2022 ;2463 251-268
      Cell-to-cell interactions between the immune and nervous systems are increasingly recognized for their importance in health and disease. Assessment of cellular neuro-immune interactions can be aided by co-culture of two (or more) cells in an in vitro model system that preserves the morphology of neuronal cells. Here we describe methods to investigate the cytotoxic effector functions of natural killer cells on sensory neurons isolated from syngeneic embryonic and adult mice. We present methods for the morphological analysis of axon fragmentation (pruning) and dynamic cell function via live confocal calcium imaging. These techniques can easily be adapted to study interactions between other combinations of immune cell subsets and neuronal populations.
    Keywords:  Axon fragmentation; Calcium imaging; Cellular cytotoxicity; Confocal microscopy; Immune synapse; Magnetic cell sorting
  11. Brain Imaging Behav. 2022 Apr 02.
      Recent neuroimaging studies have reported alterations in brain activation during cognitive tasks in cancer patients who have undergone chemotherapy treatment. However, the location of these altered brain activation patterns after chemotherapy varies considerably across studies. The aim of the present meta-analysis was to quantitatively synthesise this body of evidence using Activation Likelihood Estimation to identify reliable regions of altered brain activation in cancer patients treated with chemotherapy, compared to healthy controls and no chemotherapy controls. Our systematic search identified 12 studies that adopted task-related fMRI on non-central nervous system cancer patients who received chemotherapy relative to controls. All studies were included in the analyses and were grouped into four contrasts. Cancer patients treated with chemotherapy showed reduced activation in the left superior parietal lobe/precuneus (family-wise error corrected p < .05) compared to no chemotherapy controls. No significant clusters were found in three of our contrasts. The majority of studies did not support an association between altered brain activation and cognitive performance after chemotherapy. Findings point towards a possible chemotherapy-induced alteration, which could inform targeted treatment strategies. With continued work in this field using homogenous task-related protocols and cancer populations, fMRI may be used as a biomarker of cognitive deficits in the future.
    Keywords:  Activation Likelihood Estimation; Cancer; Chemotherapy; Cognitive deficits; Functional MRI