bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–01–01
ten papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Neuropeptide Y and its receptors in prostate cancer: associations with cancer invasiveness and perineural spread.
  2. EUS-guided celiac plexus neurolysis for pancreas cancer - Finally established or still under review?
  3. Cervical Adenocarcinoma: A Still Under-investigated Malignancy.
  4. The connection between innervation and metabolic rearrangements in pancreatic cancer through serine.
  5. Benign Neurofibroma/Schwannoma Hybrid Peripheral Nerve Sheath Tumor of the Ulnar Nerve Harboring a Metastatic Papillary Thyroid Carcinoma Deposit: A Case Report of Tumor-to-Tumor Metastasis.
  6. Young Patients With Colorectal Cancer Have Higher Early Mortality but Better Long-Term Survival.
  7. Laparoscopic excision for intrapelvic schwannoma of the sciatic nerve: A case report.
  8. Effect of Antibiotic Treatment on Attenuated Salmonella typhimurium VNP20009 Mediated Schwannoma Growth Control.
  9. Schwannomas mistaken for metastases of melanoma in PET-CT: A diagnostic challenge with consequences.
  10. Clinicopathological characteristics of gastrointestinal schwannomas: A retrospective analysis of 78 cases.
  1. J Cancer Res Clin Oncol. 2022 Dec 30.
    Neuropeptide Y and its receptors in prostate cancer: associations with cancer invasiveness and perineural spread.
    Dawid Sigorski, Wojciech Wesołowski, Agnieszka Gruszecka, Jacek Gulczyński, Piotr Zieliński, Sara Misiukiewicz, Joanna Kitlińska, Ewa Iżycka-Świeszewska.
       PURPOSE: Neuropeptide Y (NPY) is a pleiotropic peptide, which is involved in many biological mechanisms important in regulation of cell growth and survival. The aim of this study was a comprehensive analysis of the NPY system in prostate pathology.
    METHODS: The study was based on immunohistochemical analysis of NPY and its receptors, Y1R, Y2R and Y5R, in tissue samples from benign prostate (BP), primary prostate cancer (PCa) and PCa bone metastases. Tissue microarray (TMA) technique was employed, with analysis of multiple cores from each specimen. Intensity of the immunoreactivity and expression index (EI), as well as distribution of the immunostaining in neoplastic cells and stromal elements were evaluated. Perineural invasion (PNI) and extraprostatic extension (EPE) were areas of special interests. Moreover, a transwell migration assay on the LNCaP PCa cell line was used to assess the chemotactic properties of NPY.
    RESULTS: Morphological analysis revealed homogeneous membrane and cytoplasmic pattern of NPY staining in cancer cells and its membrane localization with apical accentuation in BP glands. All elements of the NPY system were upregulated in pre-invasive prostate intraepithelial neoplasia, PCa and metastases. EI and staining intensity of NPY receptors were significantly higher in PCa then in BP with correlation between Y2R and Y5R. The strength of expression of the NPY system was further increased in the PNI and EPE areas. In bone metastases, Y1R and Y5R presented high expression scores.
    CONCLUSION: The results of our study suggest that the NPY system is involved in PCa, starting from early stages of its development to disseminated states of the disease, and participates in the invasion of PCa into the auto and paracrine matter.
    Keywords:  Bone metastasis; NPY receptors (Y1R, Y2R, Y5R); Neuropeptide Y; Perineural invasion; Prostate cancer; Tumour microenvironment
    DOI:  https://doi.org/10.1007/s00432-022-04540-x
  2. Best Pract Res Clin Gastroenterol. 2022 Sep-Dec;60-61:pii: S1521-6918(22)00030-0. [Epub ahead of print]60-61 101809
    EUS-guided celiac plexus neurolysis for pancreas cancer - Finally established or still under review?
    Jonathan M Wyse, Anand V Sahai.
      Patients with pancreas cancer must deal frequently with intractable and refractory pain. Endoscopic ultrasound guided-celiac plexus neurolysis (EUS-CPN) has been the most studied and used therapeutic technique aimed to destroy the pain fibres that allow the pancreas to communicate with the central nervous system. A neurolytic agent, most commonly ethanol, is optimally spread around the celiac axis in order to reduce pain and mitigate narcotic requirements. This can be performed early to prevent the spiral of pain and medication use, or more historically as salvage therapy. Different techniques to best administer the ethanol for effective EUS-CPN are still being debated. New EUS-guided injection techniques with radiofrequency, radioactive, and/or chemotherapeutic agents need more study.
    Keywords:  Celiac plexus; Endoscopic ultrasound; Ganglia; Neurolysis; Pain; Pancreas cancer
    DOI:  https://doi.org/10.1016/j.bpg.2022.101809
  3. Anticancer Res. 2023 Jan;43(1): 53-58
    Cervical Adenocarcinoma: A Still Under-investigated Malignancy.
    Sabina Pistolesi, Giuseppe Nicolò Fanelli, Francesco Giudice, Francesca Garbini, Antonio Giuseppe Naccarato, Stefania Cosio, Marta Caretto, Angiolo Gadducci.
       BACKGROUND/AIM: The aim of the study was to correlate the expression of mismatch repairs proteins (MMR), programmed-death-ligand1 (PDL-1), and estro-progestinic receptors (ER/PgR) in tissue samples from a series of cervical adenocarcinoma (ADC) patients with their clinicopathological features.
    MATERIALS AND METHODS: Thirty-nine ADC specimens were retrospectively retrieved from the Division of Pathology of the University Hospital of Pisa from 2015 to 2021. Histological subtype, grade (G), Silva pattern, presence of lymph vascular space invasion (LVI), and perineural invasion (PNI) were annotated. On representative samples, immunostaining for ER/PgR, MLH1, PMS2, MSH2, MSH6, and PDL-1(sp142) was performed.
    RESULTS: Thirty-five ADCs were HPV-associated usual type (24 invasive and 11 in situ), 2 were clear cell type, one was a minimal deviation adenocarcinoma (MDA), and one was an invasive stratified mucin-producing carcinoma (iSMC). ADC associated with LVI were mostly G2-3, whereas those associated also with PNI were G3 with Silva pattern C. No difference in the expression of ER/PgR was observed with a dichotomic age stratification (51 years) of patients. Only 6 ADCs were MMR-deficient, all of them were of the usual type (4 invasive and 2 in situ). The heterodimer MLH-1/PMS2 was the one most frequently altered (5/6), whereas only one case had MSH6 loss. None of ADCs express PDL-1, except iSMC which showed PDL-1 expression >1% in neoplastic cells.
    CONCLUSION: Both invasive and in situ usual type ADCs indicate MMR deficiency, highlighting how this could be an early event in tumorigenesis. None of the cases, except for iSMC, express PDL-1.
    Keywords:  Cervical adenocarcinoma; MMR-deficiency; MSI; PDL-1; lymphovascular invasion
    DOI:  https://doi.org/10.21873/anticanres.16133
  4. Front Oncol. 2022 ;12 992927
    The connection between innervation and metabolic rearrangements in pancreatic cancer through serine.
    Mengmeng Dong, Lidong Cao, Ranji Cui, Yingjun Xie.
      Pancreatic cancer is a kind of aggressive tumor famous for its lethality and intractability, and pancreatic ductal adenocarcinoma is the most common type. Patients with pancreatic cancer often suffer a rapid loss of weight and abdominal neuropathic pain in their early stages and then go through cachexia in the advanced stage. These features of patients are considered to be related to metabolic reprogramming of pancreatic cancer and abundant nerve innervation responsible for the pain. With increasing literature certifying the relationship between nerves and pancreatic ductal adenocarcinoma (PDAC), more evidence point out that innervation's role is not limited to neuropathic pain but explore its anti/pro-tumor functions in PDAC, especially the neural-metabolic crosstalks. This review aims to unite pancreatic cancer's innervation and metabolic rearrangements with terminated published articles. Hopefully, this article could explore the pathogenesis of PDAC and further promote promising detecting or therapeutic measurements for PDAC according to the lavish innervation in PDAC.
    Keywords:  cancer; innervation; malignant tumors; metabolic rearrangements; pancreatic
    DOI:  https://doi.org/10.3389/fonc.2022.992927
  5. Case Rep Pathol. 2022 ;2022 9038222
    Benign Neurofibroma/Schwannoma Hybrid Peripheral Nerve Sheath Tumor of the Ulnar Nerve Harboring a Metastatic Papillary Thyroid Carcinoma Deposit: A Case Report of Tumor-to-Tumor Metastasis.
    Juan M Colazo, Alexander N Perez, Anthony D Judice, Julia Quirion, Carlos N Prieto-Granada, Ginger E Holt.
      A 74-year-old man with a medical history significant for papillary thyroid cancer (PTC) presented with a rapidly enlarging grape-sized mass in his right medial arm with paresthesia in the ulnar nerve distribution. Imaging was suspicious for a peripheral nerve sheath tumor (PNST), but an ultrasound-guided biopsy was equivocal. The mass was excised with final histopathology demonstrating a benign neurofibroma/schwannoma hybrid nerve sheath tumor (N/S HNST) harboring a metastatic PTC deposit, ultimately mimicking the rare glandular schwannoma subtype. Next-generation sequencing (NGS) of the lesion demonstrated somatic variants in BRAF and TERT (common in PTC) and NF2 (common in PNSTs). After excision, the patient's nerve symptoms improved. A postsurgical PET/CT scan also showed progression in the lungs/mediastinum. Due to the metastatic nature of his PTC, he was treated with 14 mg of Lenvima (lenvatinib) daily, and his PET/CT surveillance was performed at more frequent intervals. Tumor-to-tumor metastasis (TTM) is a rare occurrence. To our knowledge, this is the first case reported on PTC metastasizing into a benign (hybrid) PNST, which mimicked glandular schwannoma. Symptomatology, imaging characteristics, NGS, and histopathological characteristics that can decipher between different benign PNST subtypes (schwannoma, neurofibroma, glandular, hybrid, etc.), malignant PNSTs (MPNSTs), and TTM are described.
    DOI:  https://doi.org/10.1155/2022/9038222
  6. Clin Transl Gastroenterol. 2022 Dec 01. 13(12): e00543
    Young Patients With Colorectal Cancer Have Higher Early Mortality but Better Long-Term Survival.
    Shuyuan Wang, Zhen Yuan, Kemin Ni, Yixiang Zhan, Xuanzhu Zhao, Zhaoce Liu, Yanfei Liu, Ben Yi, Sizhen Lai, Xin Yin, Xingyu Zhou, Yuqi Wang, Hangyu Ping, Ran Xin, Wenhong Wang, Hongzhou Li, Yuanshun Zhao, Youkui Han, Weifeng Gao, Xinlei Jin, Guihua Wang, Zili Zhang, Guoxun Li, Qinghuai Zhang, Xipeng Zhang, Hong Ma, Chunze Zhang.
       INTRODUCTION: To define the prognosis of colorectal cancer (CRC) in young patients and to compare their postoperative treatment with that of older patients.
    METHODS: This multicenter study enrolled 5,457 patients with primary CRC who underwent surgical resection. The overall survival (OS), clinicopathologic characteristics, and postoperative treatment of 253 young patients aged 18-44 years and 5,204 older patients aged 44-80 years were analyzed.
    RESULTS: The OS rate was 77.1% for young and 74.2% for older patients (P = 0.348). Landmark analysis showed a significant difference in survival between young and older patients, with 63.8% of deaths among young patients being within 25 months of surgery compared with 42.4% among older patients (P = 0.002). Among those who survived more than 25 months, young patients had significantly better survival than older patients (P = 0.009). Multivariable analysis of young patients revealed that the tumor location, perineural invasion, and stage were associated with poor survival within 25 months; after this period, stage was the only prognostic marker. Young patients were more likely to receive chemotherapy, particularly multiagent regimens. For young patients, no significant difference in OS was found based on the chemotherapy regimen, regardless of disease stage (II, III, or IV, all P > 0.05). In addition, unlike in older patients, no difference in OS was found in young patients regardless of the drug regimen administered (all P > 0.05).
    DISCUSSION: Young-onset CRC may have a unique disease biology that warrants further research and therapy development.
    DOI:  https://doi.org/10.14309/ctg.0000000000000543
  7. Exp Ther Med. 2023 Jan;25(1): 45
    Laparoscopic excision for intrapelvic schwannoma of the sciatic nerve: A case report.
    Ruobing Wang, Shuo Li, Chang Liu, Feng Gao, Xiequn Xu, Beizhan Niu, Bin Wu.
      Schwannoma is a benign tumor of the nerve sheath originating from Schwann cells. The tumor rarely occurs in the sciatic nerve. The patient in the present case report was a 58-year-old woman presenting with pain in the right hip and leg, as well as numbness of the right lower limb. Magnetic resonance imaging revealed a solid tumor of 2.9 cm in diameter in the right pelvic space. The mass was considered to be a neurogenic tumor originating from the right sciatic nerve. Total laparoscopic surgery was performed to safely separate the tumor from the surrounding tissues, with preservation of the right sciatic nerve. The pathological result suggested a schwannoma. The patient recovered well with a transient numbness in the right heel. The laparoscopic approach used for this intrapelvic schwannoma of the sciatic nerve was safe and feasible, with the advantages of a magnified surgical field and small skin incision. However, the specific surgical approach should be based on the detailed condition of each patient and the experience of the surgeon with regard to laparoscopic surgery on benign presacral tumors and rectal tumors.
    Keywords:  case report; intrapelvic tumor; laparoscopic excision; schwannoma; sciatic nerve
    DOI:  https://doi.org/10.3892/etm.2022.11744
  8. Anticancer Res. 2023 Jan;43(1): 1-6
    Effect of Antibiotic Treatment on Attenuated Salmonella typhimurium VNP20009 Mediated Schwannoma Growth Control.
    Sherif G Ahmed, Gary J Brenner.
       BACKGROUND/AIM: This study evaluated the effect of enrofloxacin antibiotic treatment on the ability of an attenuated Salmonella typhimurium (S. typhimurium) strain VNP20009 to control schwannoma growth in a preclinical mouse schwannoma tumor model.
    MATERIALS AND METHODS: The antitumor efficacy of VNP20009 intratumoral (i.t.) injection was assessed in a syngeneic mouse-NF2 schwannoma model, with and without subcutaneous (s.c.) injection of enrofloxacin beginning on day-1 or day-8 post-VNP20009 injection. S. typhimurium colonization was assessed in excised tumor samples following antibiotic treatment.
    RESULTS: I.t. injection of the VNP20009 significantly decreased the growth of schwannoma tumors in mice compared to PBS-treated controls. Treatment of mice with enrofloxacin on day-1 post-VNP20009 injection resulted in abrogation of VNP20009-mediated tumor growth control. In contrast, tumor growth in i.t. VNP20009-injected mice infused with enrofloxacin beginning on day 8 was significantly decreased compared to i.t. PBS-injected controls. Enrofloxacin significantly reduced the number of viable VNP20009 bacteria in excised tumor samples within one day of antibiotic infusion. Viable bacteria were either few or essentially eliminated at the end of the experiment in antibiotic-treated animals compared to VNP20009-only.
    CONCLUSION: Viable VNP20009 can persist for as long as 2.5 weeks following intratumoral injection of schwannoma, during which time tumor growth is retarded. Antibiotic treatment starting 1-day following i.t. VNP20009 abrogated bacterial tumor growth control, whereas initiation of antibiotics 8-days following i.t. VNP20009 was associated with control of tumor growth, albeit less than seen in animals unexposed to antibiotics.
    Keywords:  Salmonella typhimurium (VNP20009); Schwannoma; antibiotic; bacterial cancer therapy
    DOI:  https://doi.org/10.21873/anticanres.16127
  9. Clin Case Rep. 2022 Dec;10(12): e6753
    Schwannomas mistaken for metastases of melanoma in PET-CT: A diagnostic challenge with consequences.
    Stefanie Hirsiger, Radu Olariu.
      The incidence of skin cancer and especially cutaneous malignant melanoma is rising, as are indications for staging examinations to detect metastasis. Schwannomas are common benign nerve tumors, which can be mistaken for metastasis even in highly specialized imaging. Risk of nerve lesion is high in inadvertent biopsy.
    Keywords:  FDG‐PET; cutaneous malignant melanoma; metastasis; schwannoma
    DOI:  https://doi.org/10.1002/ccr3.6753
  10. Front Oncol. 2022 ;12 1003895
    Clinicopathological characteristics of gastrointestinal schwannomas: A retrospective analysis of 78 cases.
    Hailing Peng, Liu Han, Yuyong Tan, Yi Chu, Liang Lv, Deliang Liu, Hongyi Zhu.
       Introduction: Schwannomas are tumors arising from Schwan cells of the neural sheath, which rarely occur in the gastrointestinal tract. The aim of the present study was to analyze the clinicopathological features and treatment outcomes of gastrointestinal schwannomas (GISs).
    Methods: Patients who were diagnosed with GISs in our hospital from January 2010 to December 2021 were selected. Data about demographic characteristics, clinical symptoms, treatment methods and outcomes, pathological results, and follow-up results were retrospectively collected and analyzed.
    Results: A total of 78 patients with 79 GISs were included, the female-to-male ratio was 55:23, and the average age was 52.12 ± 12.26 years. One-third (26/78) of the patients were asymptomatic. A total of 79 GISs were removed, and the average size was 3.63 ± 2.03 cm (range, 0.3-10 cm). As for tumor location, 54 GISs were located in the stomach, 14 in the esophagus, 2 in the duodenum, 6 in the colorectum (4 in the colon and 2 in the rectum), and the other 3 in the small intestine. A total of 23 and 55 patients underwent endoscopic and surgical resections, respectively. Compared with surgical resection, endoscopic resection is associated with a smaller diameter, lower cost, and shorter hospital stay. Pathological results revealed that S100 was positive in all the GISs. No recurrence was noticed during a median follow-up of 45 months (range, 6-148 months).
    Conclusion: GISs are rare gastrointestinal tumors with favorable prognoses, which are most commonly seen in the stomach and diagnosed by pathological findings with immunohistochemical staining. Surgical resection remains the standard method for removing GISs, while endoscopic resection may serve as an alternative method for selected patients with GISs and may be attempted in GISs with a diameter of <3 cm and no signs of malignancy.
    Keywords:  endoscopic therapy; gastrointestinal schwannomas; prognosis; submucosal tumors; surgical treatment
    DOI:  https://doi.org/10.3389/fonc.2022.1003895
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