bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2021‒11‒28
eight papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute
  1. Sympathetic signaling facilitates progression of neuroendocrine prostate cancer.
  2. Factors Predicting Nodal Metastasis in Penile Cancer: Analysis from a Tertiary Center.
  3. A novel method for predicting perineural invasion of distal cholangiocarcinoma on multidetector-row computed tomography.
  4. Hide-and-seek: Neurotropic squamous cell carcinoma of the periorbital region - a series of five cases and review of the literature.
  5. The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma.
  6. Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology.
  7. High Annexin A10 expression is correlated with poor prognosis in pancreatic ductal adenocarcinoma.
  8. Reviewing Schwannoma-Hemangioma Composite Tumors With Their Tumorigenetic Molecular Pathways and Associated Syndromic Manifestations.
  1. Cell Death Discov. 2021 Nov 22. 7(1): 364
    Sympathetic signaling facilitates progression of neuroendocrine prostate cancer.
    Shubham Dwivedi, Maricris Bautista, Sanskriti Shrestha, Hussain Elhasasna, Tanaya Chaphekar, Frederick S Vizeacoumar, Anand Krishnan.
      The progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently shown to promote PC. However, their contribution to NEPC was not studied well. In this study, we explored whether sympathetic neurosignaling contributes to NED. We found that human prostate tumors from patients that later developed metastases and castration-resistant prostate cancer (CRPC), a stage preceding to NEPC, have high sympathetic innervations. Our work revealed that high concentrations of the sympathetic neurotransmitter norepinephrine (NE) induces NED-like changes in PC cells in vitro, evident by their characteristic cellular and molecular changes. The NE-mediated NED was effectively inhibited by the Adrβ2 blocker propranolol. Strikingly, propranolol along with castration also significantly inhibited the development and progression of NEPC in vivo in an orthotopic NEPC model. Altogether, our results indicate that the NE-Adrβ2 axis is a potential therapeutic intervention point for NEPC.
    DOI:  https://doi.org/10.1038/s41420-021-00752-1
  2. Urol Int. 2021 Nov 24. 1-6
    Factors Predicting Nodal Metastasis in Penile Cancer: Analysis from a Tertiary Center.
    Kanuj Malik, Deepak Chandrasekaran, Narayanaswamy Kathiresan, Anand Raja.
      INTRODUCTION: Lymph node metastasis is an important prognostic marker in penile cancer. Identification of occult metastasis is by lymphadenectomy based on the histological features of primary tumor; however, this leads to unnecessary surgical morbidity in node negative patients.METHODS: A retrospective analysis of all surgically treated penile cancer patients managed at our institute from January 2011 to March 2014 was performed. Patient characteristics, histological factors, and lymph node involvement were identified. Logistic regression analysis was used to compute odds ratio (OR) in univariate and multivariate analysis.
    RESULTS: Ninety seven patients underwent surgical management at our institute during the abovementioned period. Grade III tumor, presence of lymphovascular invasion, tumor thickness >10 mm, perineural invasion (PNI) and Ki67 >50% were significantly associated with nodal metastasis. On multivariate analysis, only presence of PNI was found to be significant (OR: 6.82) (95% confidence interval: 1.72-27.03) (p = 0.006).
    CONCLUSION: PNI is a strong independent predictor of occult lymph node metastasis in penile cancers. Its inclusion in stratification of clinically node negative patients will identify high-risk patients who will benefit from prophylactic lymphadenectomy.
    Keywords:  Cancer; Lymphatic metastasis; Penile neoplasm; Risk factors
    DOI:  https://doi.org/10.1159/000519918
  3. Surg Today. 2021 Nov 24.
    A novel method for predicting perineural invasion of distal cholangiocarcinoma on multidetector-row computed tomography.
    Ryusei Yamamoto, Teiichi Sugiura, Yukiyasu Okamura, Ryo Ashida, Katsuhisa Ohgi, Mihoko Yamada, Shimpei Otsuka, Takeshi Aramaki, Koiku Asakura, Katsuhiko Uesaka.
      PURPOSE: Excessive perineural invasion (PNI) is associated with a high risk of radial margin (RM) positivity and a poor prognosis for patients with distal cholangiocarcinoma (DCC). This study evaluates a new method of predicting the extent of PNI preoperatively.METHODS: The subjects of this retrospective study were 201 patients who underwent resection for DCC between 2002 and 2018. This study identified the 'periductal enation sign' (PES), defined as the surrounding soft tissue enhancement that appears as an enation from the circumference of the enhanced extrahepatic bile duct on multidetector-row computed tomography (MDCT) scans, as a predictor of PNI. We analyzed the outcomes of the patients in relation to the presence or absence of the PES on MDCT scans.
    RESULTS: The PES in the PNI-positive group was significantly longer than that in the PNI-negative group. As the length of the PES extended, the grade of PNI increased. A positive PES was defined as a PES length of ≥ 2.0 mm. Patients with a positive PES were more frequently positive for RM (23.7% vs. 2.1%) and locoregional recurrence (23.7% vs. 6.3%) and exhibited significantly poorer overall survival than those with a negative PES (30.2% vs. 54.6% at 5 years).
    CONCLUSIONS: The presence and extent of PNI can be predicted easily and effectively by the PES length. A positive PES was associated with poor local controllability and a poor prognosis.
    Keywords:  Borderline resectable; Computed tomography; Distal cholangiocarcinoma; Perineural invasion
    DOI:  https://doi.org/10.1007/s00595-021-02405-3
  4. J Dtsch Dermatol Ges. 2021 Nov;19(11): 1571-1580
    Hide-and-seek: Neurotropic squamous cell carcinoma of the periorbital region - a series of five cases and review of the literature.
    Evi M Morandi, Tina Rauchenwald, Petra Puelzl, Bernhard W Zelger, Bettina G Zelger, Benjamin Henninger, Gerhard Pierer, Dolores Wolfram.
      Squamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun-exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology. Aside from presenting five challenging cases, this work analyzes risk factors, clinical as well as histological features, and treatment options for periorbital squamous cell carcinoma with perineural invasion.
    DOI:  https://doi.org/10.1111/ddg.14582
  5. BMC Cancer. 2021 Nov 20. 21(1): 1254
    The neuropeptide calcitonin gene-related peptide links perineural invasion with lymph node metastasis in oral squamous cell carcinoma.
    Yu Zhang, Mingtao Chen, Zheqi Liu, Xu Wang, Tong Ji.
      OBJECTIVE: Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed.MATERIALS AND METHODS: The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells.
    RESULTS: OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P < 0.0001, n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P < 0.0001), and were correlated with LNM (P < 0.0001) and PNI (P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor.
    CONCLUSIONS: The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.
    Keywords:  Calcitonin gene-related peptide; Lymph node metastasis; Oral squamous cell carcinoma; Perineural invasion
    DOI:  https://doi.org/10.1186/s12885-021-08998-9
  6. HPB (Oxford). 2021 Nov;pii: S1365-182X(21)00104-0. [Epub ahead of print]23(11): 1666-1673
    Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology.
    Stefano Crippa, Giulio Belfiori, Massimiliano Bissolati, Stefano Partelli, Michele Pagnanelli, Domenico Tamburrino, Giulia Gasparini, Corrado Rubini, Giuseppe Zamboni, Massimo Falconi.
      BACKGROUND: Current treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are related with overall and early recurrence after pancreatectomy for PDAC.METHODS: Retrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence.
    RESULTS: 261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3-4 Clavien-Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3-4 Clavien-Dindo complications (OR: 3.05) were independent risk factors for early recurrence.
    CONCLUSION: Although overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.
    DOI:  https://doi.org/10.1016/j.hpb.2021.04.004
  7. Histol Histopathol. 2021 Nov 25. 18397
    High Annexin A10 expression is correlated with poor prognosis in pancreatic ductal adenocarcinoma.
    Akira Ishikawa, Kazuya Kuraoka, Junichi Zaitsu, Akihisa Saito, Atsushi Yamaguchi, Toshio Kuwai, Takeshi Sudo, Naoto Hadano, Hirotaka Tashiro, Kiyomi Taniyama, Wataru Yasuif.
      Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death. Owing to its poor prognosis, new molecular biomarkers for PDAC are needed. Annexin A10 (ANXA10) is a calcium-/phospholipid-binding protein belonging to the annexin family of proteins. ANXA10 is not only associated with gastric phenotypes, but also acts an independent prognostic factor in several cancers. However, the role of ANXA10 in PDAC remains unknown. Therefore, we examined the relationship between ANXA10 and the prognosis of PDAC. We analyzed the expression of ANXA10 using data from public databases, and performed immunohistochemistry analysis for 81 PDAC cases. We then investigated the relationship between ANXA10 expression and clinicopathological features. ANXA10 was detected in 47 of 81 PDAC cases (58%). High expression of ANXA10 was significantly related to poor overall survival (OS; p=0.011). Univariate analysis of OS revealed three prognostic parameters: tumor grade (p=0.046), perineural invasion (p=0.017), and ANXA10 expression (p=0.012). Multivariate analysis indicated that ANXA10 expression (p<0.01) alone was a prognostic factor in PDAC cases. Our findings suggest that ANXA10 expression is an independent prognostic factor in PDAC cases and shows promise as a new biomarker in PDAC.
    DOI:  https://doi.org/10.14670/HH-18-397
  8. Cureus. 2021 Nov;13(11): e19839
    Reviewing Schwannoma-Hemangioma Composite Tumors With Their Tumorigenetic Molecular Pathways and Associated Syndromic Manifestations.
    Subramaniam Ramkumar.
      Schwannomas are common peripheral nerve sheath tumors. Cavernous hemangiomas are vascular tumors that can affect any organ system. The coexistence of cavernous hemangioma with peripheral nervous system neoplasms is a rare occurrence. So far, 37 cases have been documented, and they have been divided into two categories: conjoined association (neoplasms discovered within the tumor tissue) and discrete association (neoplasms discovered outside the tumor tissue, thus placing neoplasms and tumors in close proximity but in different locations). Schwannomas and neurofibromas are the most prevalent tumors linked to cavernous hemangiomas that have been documented. The author provides a comprehensive review of all such cases published in the past with an emphasis on the implications of their tumorigenetic molecular pathways and syndromic manifestations.
    Keywords:  angiopoitein; hamartin; hemangioma; merlin; schwannoma; tie 2; tuberin; tuberous sclerosis; vegf
    DOI:  https://doi.org/10.7759/cureus.19839
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