bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–01–29
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute



  1. Dev Cell. 2023 Jan 23. pii: S1534-5807(22)00893-0. [Epub ahead of print]58(2): 81-93
      Similar to their pivotal roles in nervous system development, neurons have emerged as critical regulators of cancer initiation, maintenance, and progression. Focusing on nervous system tumors, we describe the normal relationships between neurons and other cell types relevant to normal nerve function, and discuss how disruptions of these interactions promote tumor evolution, focusing on electrical (gap junctions) and chemical (synaptic) coupling, as well as the establishment of new paracrine relationships. We also review how neuron-tumor communication contributes to some of the complications of cancer, including neuropathy, chemobrain, seizures, and pain. Finally, we consider the implications of cancer neuroscience in establishing risk for tumor penetrance and in the design of future anti-tumoral treatments.
    Keywords:  T cells; brain tumors; glioma; microglia; nerves; neuronal activity; neurotransmitter; synapse
    DOI:  https://doi.org/10.1016/j.devcel.2022.12.011
  2. Gynecol Oncol Rep. 2023 Feb;45 101136
      Neurological paraneoplastic syndromes are a rare subgroup of diseases commonly related to neuroendocrine tumors. However, they have been associated with uterine malignancies (sarcomas, endometrial carcinomas, and neuroendocrine cancers). Their presentation often correlates with a cancer diagnosis or cancer recurrence underlining their clinical significance. The most common neurological paraneoplastic syndrome in uterine cancer is cerebral degeneration with a comprehensive clinical presentation of pancerebral dysfunction. However, other neurological syndromes present with various symptoms leading to delayed diagnosis. Less common paraneoplastic neurological syndromes associated with uterine cancer are encephalitis, encephalomyelitis, subacute sensory neuropathy, sensory-motor neuropathy, dermatomyositis, cancer-associated retinopathy, opsoclonus, Guillain-Barre syndrome, necrotizing myopathy, and stiff-person syndrome. Herein, we reviewed published cases of neurological paraneoplastic syndromes in uterine cancer in order to raise awareness of these rare syndromes. We recorded patients' clinical presentation, antibodies detected, treatment, and clinical outcomes.
    Keywords:  Cancer; Endometrial; Gynaecological; Neurological; Paraneoplastic syndrome; Uterine
    DOI:  https://doi.org/10.1016/j.gore.2023.101136
  3. J Biomed Sci. 2023 Jan 28. 30(1): 8
      Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells. Current clinical evidences also suggest that chronic stress affects the outcome of cancer treatment. However, in clinic, there is lack of effective treatment for chronic stress in cancer patients. In this review, we discuss the main mechanisms by which chronic stress regulates the tumor microenvironment, including functional regulation of tumor cells by stress hormones (stem cell-like properties, metastasis, angiogenesis, DNA damage accumulation, and apoptotic resistance), metabolic reprogramming and immune escape, and peritumor neuromodulation. Based on the current clinical treatment framework for cancer and chronic stress, we also summarize pharmacological and non-pharmacological therapeutic approaches to provide some directions for cancer therapy.
    Keywords:  Cancer treatment; Chronic stress; Tumor development; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12929-023-00903-9
  4. Front Oncol. 2022 ;12 1070878
       Objective: Peripheral nerve sheath tumors (PNST) include mainly schwannomas and neurofibromas. Surgical resection represents the mainstay of treatment but due to their pathogenesis, distinguishing between intact functional nerve and the fibers from whence the PNST arose may not always be easy to perform, constituting the most relevant risk factor in determining a worsening in neurological condition. The introduction of intraoperative tools to better visualize these tumors could help achieve a gross-total resection. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of a large cohort of PNST.
    Methods: Between September 2018 and December 2021, 142 consecutive patients harboring a suspected PNST underwent fluorescein-guided surgery at the Department of Neurosurgery of the Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. All patients presented with a different degree of contrast enhancement at preoperative MRI. SF was intravenously injected after intubation at 1 mg/kg. Intraoperative fluorescein characteristics and postoperative neurological and radiological outcomes were collected, analyzed, and retrospectively compared with a historical series.
    Results: 142 patients were included (42 syndromic and 100 sporadic); schwannoma was the predominant histology, followed by neurofibroma (17 neurofibroma e 12 plexiform neurofibroma) and MPNST. Bright fluorescence was present in all cases of schwannomas and neurofibromas, although with a less homogeneous pattern, whereas it was significantly less evident for malignant PNST; perineurioma and hybrid nerve sheath tumors were characterized by a faint fluorescence enhancement. The surgical resection rate in the general population and even among the subgroups was about 66.7%; from the comparative analysis, we found a consistently higher rate of complete tumor removal in plexiform neurofibromas, 66% in the "fluorescent" group vs 44% in the "historical" group (p-value < 0.05). The rate of complications and mean surgical time were superimposable among the two populations.
    Conclusions: SF is a valuable method for safe fluorescence-guided PNST and mimicking lesions resection. Our data showed a positive effect of fluorescein-guided surgery in increasing the rate of surgical resection of plexiform neurofibromas, suggesting a possible role in improving the functional and oncological outcome of these lesions.
    Keywords:  PNST; YELLOW560 filter; fluorescein-guided surgery; neurofibroma; peripheral nerve sheath tumors; schwannoma; sodium fluorescein (SF)
    DOI:  https://doi.org/10.3389/fonc.2022.1070878
  5. Lung India. 2023 Jan-Feb;40(1):40(1): 70-74
      Schwannomas are benign slow-growing tumours arising from the Schwann cells of the nerve sheath. They may arise anywhere in the course of the nerves in the body. The clinical presentations are non-specific, and when present in rare locations such as lungs, the diagnosis becomes difficult. The present case series describes the clinical presentation and diagnosis of five cases of lung schwannoma. The diagnosis was mainly assisted by the immuno-histochemical examination comprising markers such as S-100, Calretinin, CD34, CD56, Desmin, and EMA. A definitive diagnosis of benign nerve tumours in such rare locations may help in better pre-operative assessment and surgery for complete recovery of the patients.
    Keywords:  Lung; pulmonary; schwannomas
    DOI:  https://doi.org/10.4103/lungindia.lungindia_197_22
  6. Front Surg. 2022 ;9 1020240
       Introduction: The effect of liver margin on colorectal cancer liver metastases (CRLM) after hepatectomy has been controversial. In this study, we conducted a postoperative follow-up study of 205 patients with CRLM to clarify whether a positive margin is significant and to define the risk factors affecting CRLM survival.
    Methods: The data of 205 patients with CRLM who underwent surgical treatment at the Third Hospital of Peking University in the Department of General Surgery from January 2009 to December 2020 were retrospectively analyzed. The general data, surgical data and postoperative follow-up of the patients were statistically analyzed.
    Results: There were 130 cases (63.4%) of R0 resection and 75 cases (36.6%) of R1 resection. There were 136 males and 69 females, age 61 ± 11 years, and body mass index (BMI 24.5 ± 3.3 kg/m2). The overall survival rates at 1, 3, and 5 years for the entire cohort were 93.4%, 68.4%, and 45.5% in the R0 resection group vs. 93.2%, 53.7%, and 42% in the R1 resection group, respectively, which were not statistically significant (P = 0.520). The 1-, 3-, and 5-year disease-free survival rates of 63.2%, 33.3%, and 29.7% were significantly better in the R0 resection group than in the R1 resection group of 47.9%, 22.7%, and 17.7% (P = 0.016), respectively. After multivariable analysis, carbohydrate antigen 19-9 (CA19-9) > 39 U/ml (HR = 2.29, 95% CI: 1.39-3.79, P = 0.001), primary tumor perineural invasion (HR = 1.78, 95% CI: 1.01-3.13, P = 0.047), and BMI > 24 kg/m2 (HR = 1.75, 95% CI: 1.05-2.93, P = 0.033) were independently associated with poorer overall patient survival. The number of liver metastases >2 (HR = 1.65, 95% CI: 1.10-2.47, P = 0.016), the maximum diameter of metastases ≥50 mm (HR = 1.67, 95% CI: 1.06-2.64, P = 0.026), and vascular invasion of the primary tumor (HR = 1.65, 95% CI: 1.03-2.64, P = 0.038) were also independently associated with poorer disease-free survival.
    Conclusion: In patients undergoing hepatectomy for CRLM, the negative effect of the R1 margin should be downplayed, and although the disease-free survival of the R1 margin is shorter than that of the R0 margin, it has no impact on overall survival. To improve overall survival, extra attention should be given to the factors of preoperative BMI, preoperative CA19-9, and the presence of perineural invasion of the primary tumor.
    Keywords:  BMI; CA19-9; R1 margin; colorectal cancer; hepatectomy; liver metastasis
    DOI:  https://doi.org/10.3389/fsurg.2022.1020240
  7. Medicine (Baltimore). 2023 Jan 20. 102(3): e32696
       RATIONALE: Type 1 neurofibromatosis (NF1) is one of the most prevalent genetic conditions. NF1 is characterized by cutaneous plexiform neurofibromas and café au lait skin pigmentation, and is inherited in an autosomal dominant trait with mutation in the neurofibromin 1 gene on chromosome 17. Neurofibromin is involved in Ras proto-oncogene regulation. Accordingly, NF1 may lead to malignancies, with a lifetime cancer risk of 60%. Malignant peripheral nerve sheath tumor (MPNST) is the leading cause of mortality due to NF1. The relevance of gastrointestinal stromal tumor (GIST) in NF1 is increasingly being reported in the literature and NF1-associated GIST has been identified to have an alternative molecular pathogenesis.
    PATIENT CONCERNS: A 62-years-old female had a 7 × 5 cm growing back mass in the background of various sized cutaneous neurofibromas with café au lait spots. Computed tomography performed in the workup revealed a 4.1 cm enhancing mass near the ileal mesentery.
    DIAGNOSES: NF1 affected by cutaneous MPNST of the back, and synchronous GIST and submucosal angiomyolipoma (AML) of the jejunum.
    INTERVENTIONS: The patient underwent laparoscopic jejunal mass excision, and excision and flap coverage for the back mass owing to the suspicion of multiple MPNSTs. However, the abdominal masses were diagnosed as GIST and AML following confirmation of the immunohistochemical profiles. Accordingly, the patient was administered adjuvant radiotherapy to the MPNST after surgery.
    OUTCOMES: Symptomatic improvements were achieved, and no subsequent relapses were observed.
    LESSONS: Although MPNST and GIST are not rare neoplasm in NF1, only 2 case reports have been published on the synchronous occurrence of these tumors. Moreover, no case report has been published on AML in NF1, except 1 renal AML in segmental neurofibromatosis. Identifying the clinical and pathologic significances of the NF1 is important to achieve improved diagnostic accuracy.
    DOI:  https://doi.org/10.1097/MD.0000000000032696
  8. Radiol Case Rep. 2023 Mar;18(3): 1076-1078
      Schwannomas are a type of benign tumor that affects the nerve sheath, commonly located in the head and neck. However, Schwannomas in the hepatoduodenal ligament are extremely rare. The case was a 38-year-old female presented with a 2-month history of abdominal pain in the right upper quadrant and 2 weeks of exacerbation. Computed Tomography revealed a solid mass with target-like enhancement in the hepatoduodenal ligament. She underwent complete surgical excision, and a histopathological examination confirmed the mass as a schwannoma. This case highlights the importance of anatomical location and CT features for diagnosis of schwannoma in the hepatoduodenal ligament.
    Keywords:  Case report; Computed tomography; Hepatoduodenal ligament; Schwannoma
    DOI:  https://doi.org/10.1016/j.radcr.2022.12.032