bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2022‒09‒04
six papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute



  1. Nat Rev Gastroenterol Hepatol. 2022 Sep 02.
      Maintenance of gastrointestinal health is challenging as it requires balancing multifaceted processes within the highly complex and dynamic ecosystem of the gastrointestinal tract. Disturbances within this vibrant environment can have detrimental consequences, including the onset of gastrointestinal cancers. Globally, gastrointestinal cancers account for ~19% of all cancer cases and ~22.5% of all cancer-related deaths. Developing new ways to more readily detect and more efficiently target these malignancies are urgently needed. Whereas members of the tumour microenvironment, such as immune cells and fibroblasts, have already been in the spotlight as key players of cancer initiation and progression, the importance of the nervous system in gastrointestinal cancers has only been highlighted in the past few years. Although extrinsic innervations modulate gastrointestinal cancers, cells and signals from the gut's intrinsic innervation also have the ability to do so. Here, we shed light on this thriving field and discuss neural influences during gastrointestinal carcinogenesis. We focus on the interactions between neurons and components of the gastrointestinal tract and tumour microenvironment, on the neural signalling pathways involved, and how these factors affect the cancer hallmarks, and discuss the neural signatures in gastrointestinal cancers. Finally, we highlight neural-related therapies that have potential for the management of gastrointestinal cancers.
    DOI:  https://doi.org/10.1038/s41575-022-00669-9
  2. Neurotherapeutics. 2022 Sep 02.
      Genetic syndromes which develop one or more nervous system (NS) tumors as one of the manifestations can be grouped under the umbrella term of NS tumor predisposition syndromes. Understanding the underlying pathological pathways at the molecular level has led us to many radical discoveries, in understanding the mechanisms of tumorigenesis, tumor progression, interactions with the tumor microenvironment, and development of targeted therapies. Currently, at least 7-10% of all pediatric cancers are now recognized to occur in the setting of genetic predisposition to cancer or cancer predisposition syndromes. Specifically, the cancer predisposition rate in pediatric patients with NS tumors has been reported to be as high as 15%, though it can approach 50% in certain tumor types (i.e., choroid plexus carcinoma associated with Li Fraumeni Syndrome). Cancer predisposition syndromes are caused by pathogenic variation in genes that primarily function as tumor suppressors and proto-oncogenes. These variants are found in the germline or constitutional DNA. Mosaicism, however, can affect only certain tissues, resulting in varied manifestations. Increased understanding of the genetic underpinnings of cancer predisposition syndromes and the ability of clinical laboratories to offer molecular genetic testing allows for improvement in the identification of these patients. The identification of a cancer predisposition syndrome in a CNS tumor patient allows for changes to medical management to be made, including the initiation of cancer surveillance protocols. Finally, the identification of at-risk biologic relatives becomes feasible through cascade (genetic) testing. These fundamental discoveries have also broadened the horizon of novel therapeutic possibilities and have helped to be better predictors of prognosis and survival. The treatment paradigm of specific NS tumors may also vary based on the patient's cancer predisposition syndrome and may be used to guide therapy (i.e., immune checkpoint inhibitors in constitutional mismatch repair deficiency [CMMRD] predisposition syndrome) [8]. Early diagnosis of these cancer predisposition syndromes is therefore critical, in both unaffected and affected patients. Genetic counselors are uniquely trained master's level healthcare providers with a focus on the identification of hereditary disorders, including hereditary cancer, or cancer predisposition syndromes. Genetic counseling, defined as "the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease" plays a vital role in the adaptation to a genetic diagnosis and the overall management of these diseases. Cancer predisposition syndromes that increase risks for NS tumor development in childhood include classic neurocutaneous disorders like neurofibromatosis type 1 and type 2 (NF1, NF2) and tuberous sclerosis complex (TSC) type 1 and 2 (TSC1, TSC2). Li Fraumeni Syndrome, Constitutional Mismatch Repair Deficiency, Gorlin syndrome (Nevoid Basal Cell Carcinoma), Rhabdoid Tumor Predisposition syndrome, and Von Hippel-Lindau disease. Ataxia Telangiectasia will also be discussed given the profound neurological manifestations of this syndrome. In addition, there are other cancer predisposition syndromes like Cowden/PTEN Hamartoma Tumor Syndrome, DICER1 syndrome, among many others which also increase the risk of NS neoplasia and are briefly described. Herein, we discuss the NS tumor spectrum seen in the abovementioned cancer predisposition syndromes as with their respective germline genetic abnormalities and recommended surveillance guidelines when applicable. We conclude with a discussion of the importance and rationale for genetic counseling in these patients and their families.
    Keywords:  Brain tumor; Cancer genetics; Cancer predisposition syndromes; Nervous system surveillance of genetic syndromes
    DOI:  https://doi.org/10.1007/s13311-022-01277-w
  3. Hum Cell. 2022 Sep 02.
      Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.
    Keywords:  Concurrent chemoradiotherapy; Immunohistochemical staining; Prognostic marker; Rectal cancer; Serine peptidase inhibitor Kazal type-1
    DOI:  https://doi.org/10.1007/s13577-022-00776-4
  4. Nutr Cancer. 2022 Sep 02. 1-10
      The impact of body composition (BC) on the prognosis of resected intrahepatic cholangiocarcinoma (ICC) has been poorly studied. Aims: i) to evaluate the prevalence of low muscle mass (MM) in patients; ii) to assess the impact of BC on patient overall survival (OS) and disease-free survival (DFS), and iii) on the incidence of postoperative complications. All consecutive patients who underwent liver resection for ICC between 2004 and 2016 and who had preoperative CT scans were included. Ninety-three patients were included. Sixty percent (55/91) had low total MM. On multivariable analysis, high visceral fat (HR 2.48, CI95% [1.63; 3.77], p < 0.0001), nodules >1 (HR 3.15 [1.67; 5.93], p = 0.0004), involvement adjacent organ (HR 6.67 [1.88; 23.69], p = 0.003), and postoperative sepsis (HR 3.04 [1.54; 5.99], p = 0.0013) were independently associated with OS. High visceral fat (HR 2.10 [1.31; 3.38], p = 0.002], nodules >1 (HR 3.01, [1.49; 6.10], p = 0.002), postoperative sepsis (HR 5.16 [2.24; 11.89], p = 0.0001), ASA score (p = 0.02) and perineural invasion (HR 3.30 [1.62; 6.76], p = 0.001) were independently associated with lower DFS. Conclusion: 60% of ICC patients had low MM before surgery. High visceral fat, but not muscle mass, was an independent prognostic factor for poor OS and DFS in European patients with resected ICC.
    DOI:  https://doi.org/10.1080/01635581.2022.2117387
  5. Chirurgia (Bucur). 2022 Jun;pii: 11. [Epub ahead of print]117(4): 454-462
      Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic tumor, known for an aggressive evolution. Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor, considered a premalignant lesion with the possibility of carcinogenesis towards PDAC. The clinical, surgical and histopathological particularities of the association between PDAC and IPMN are yet unknown, further research being needed. Methods: We have conducted a retrospective descriptive study, on a nine-year period (2012-2020), with the aim of comparing the characteristics of patients that underwent curative surgical interventions for solitary PDAC and PDAC associated to IPMN. Results: Fifteen patients with PDAC associated with IPMN (Group 1) and 386 patients with solitary PDAC (Group 2) were included in our study. Group 1 had a younger average age (61.8 years) compared to Group 2 (63.89 years). Total pancreatectomy was more frequently performed for Group 1 than Group 2 (33.33% vs 12.43%). Group 1 had a higher percentage of cases with positive perineural, perilymphatic and perivascular invasion. Group 1 registered a worse overall survival, as well as a worse short-time survival compared to Group 2. Conclusions: PDAC associated to IPMN registers distinct epidemiological, clinical and histopathological characteristics compared to solitary PDAC.
    Keywords:  intraductalpapillarymucinousneoplasm; pancreaticadenocarcinoma; pancreaticcancer; pancreaticsurgery
    DOI:  https://doi.org/10.21614/chirurgia.2760
  6. Heliyon. 2022 Aug;8(8): e10286
      Schwannomas are mostly benign tumors arising from the nerve sheath. These tumors can be found anywhere in the body. Depending on their locations, they may cause compressive symptoms as well as cosmetic or functional defects. Ancient schwannomas, the rare variant of schwannomas, are the slow-growing tumors characterized with cystic necrotic degeneration areas in the neoplastic tissue. Ancient schwannomas rarely occur in the spinal canal, they are particularly unusual in the thoracic spine. Herein we present a 66-year-old woman with chronic back pain who is detected a cystic mass in her thoracic spine by magnetic resonance imaging and is diagnosed with ancient schwannoma by histological examination.
    Keywords:  Ancient Schwannoma; Spinal cord compression; Thoracic spine
    DOI:  https://doi.org/10.1016/j.heliyon.2022.e10286