bims-netuvo 2022-03-13 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2022–03–13
seven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Neural Signaling in Cancer.
Sympathetic nervous signaling dictates prostate cancer progression.
The association between perineural invasion in mpMRI-targeted and/or systematic prostate biopsy and adverse pathological outcomes in robot-assisted radical prostatectomy.
Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study.
[Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection].
Clinicopathologic and Molecular Study of Hybrid Nerve Sheath Tumors Reveals Their Common Association With Fusions Involving VGLL3.
Long-Term Feasibility of 13.56 MHz Modulated Electro-Hyperthermia-Based Preoperative Thermoradiochemotherapy in Locally Advanced Rectal Cancer.

Annu Rev Neurosci. 2022 Feb 08.

Neural Signaling in Cancer.

Michael B Keough, Michelle Monje.

Nervous system activity regulates development, homeostasis, and plasticity of the brain as well as other organs in the body. These mechanisms are subverted in cancer to propel malignant growth. In turn, cancers modulate neural structure and function to augment growth-promoting neural signaling in the tumor microenvironment. Approaching cancer biology from a neuroscience perspective will elucidate new therapeutic strategies for presently lethal forms of cancer. In this review, we highlight the neural signaling mechanisms recapitulated in primary brain tumors, brain metastases, and solid tumors throughout the body that regulate cancer progression. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

DOI: https://doi.org/10.1146/annurev-neuro-111020-092702
Cell Death Discov. 2022 Mar 10. 8(1): 109

Sympathetic nervous signaling dictates prostate cancer progression.

D Sigorski, E Iżycka-Świeszewska.

DOI: https://doi.org/10.1038/s41420-022-00928-3
Actas Urol Esp (Engl Ed). 2022 Mar 05. pii: S2173-5786(22)00011-7. [Epub ahead of print]

The association between perineural invasion in mpMRI-targeted and/or systematic prostate biopsy and adverse pathological outcomes in robot-assisted radical prostatectomy.

N Karsiyakali, M Bulent Ozgen, B Ozveren, C Akbal, A Dincer, H Durak, L Turkeri.

   INTRODUCTION AND OBJECTIVES: This study aims to investigate the relationship between perineural invasion (PNI) in targeted (TBx) and/or systematic (SBx) prostate needle biopsy and adverse pathological features of prostate cancer (PCa) in prostatectomy specimens.
MATERIALS AND METHODS: A total of 95 male patients who underwent transperineal TBx and/or concomitant SBx subsequently treated with robot-assisted radical prostatectomy for PCa between October 2015 and June 2020 were included. The performance of PNI as a classification test (sensitivity, specificity, positive and negative predictive values) and its correlation with clinically significant PCa, surgical margin positivity, extraprostatic extension, and seminal vesicle invasion in prostatectomy were computed.
RESULTS: The median age of the patients was 65 (60-70) years. TBx and concomitant SBx were performed in 78 (82.1%) patients, while 16 (16.8%) patients underwent SBx alone and one (1.1%) patient underwent TBx alone. The frequency of PNI in TBx and SBx was 17 (21.5%) and 32 (34.0%), respectively. The specificity/negative predictive values of PNI for surgical margin positivity, extraprostatic extension, and seminal vesicle invasion were 79.7/88.7%, 92.5/79.0%, and 83.3/96.8%, in TBx, and 71.1/87.1%, 80.7/74.2%, and 69.5/91.9%, in SBx, respectively. There was also a statistically significant correlation between PNI in biopsy and surgical margin positivity, extraprostatic extension, and seminal vesicle invasion in prostatectomy as well as the ISUP grade group and pT stage.
CONCLUSIONS: The absence of PNI in prostate needle biopsy may predict localized PCa with a pT stage ≤ 2c and negative surgical margins in contrast to its presence which appears to be an indicator of unfavorable factors in final pathology.

Keywords:  Biopsia de próstata por fusión RMmp/ecografía; Extensión extraprostática; Extraprostatic extension; Invasión perineural; Invasión vesículas seminales; Perineural invasion; Prostatectomía radical; Radical prostatectomy; Seminal vesicle invasion; mpMRI/TRUS fusion prostate biopsy

DOI:  https://doi.org/10.1016/j.acuroe.2022.02.004
PeerJ. 2022 ;10 e12974

Influence of Lymphangio vascular (V) and perineural (N) invasion on survival of patients with resected esophageal squamous cell carcinoma (ESCC): a single-center retrospective study.

Chengke Xie, Zhiyao Chen, Jie Xu, Zhiyong Meng, Zhijun Huang, Jianqing Lin.

   Background: Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship between LVI/PNI and survival of esophageal squamous cell carcinoma (ESCC) is still unclear. We aim to demonstrate the prognostic significance of LVI/PNI in ESCC.
Methods: A total of 195 ESCC patients underwent curative surgery from 2012 to 2018 was collected in the 2nd Affiliated Hospital of Fujian Medical University. All the patients were divided into four groups based on the status of the neurovascular invasion: (1) neither LVI nor PNI (V0N0); (2) LVI alone (V1N0); (3) PNI alone (V0N1); (4) combined LVI and PNI (V1N1). First, the analysis included the Kaplan-Meier survival estimates with the Log rank test were performed to determine median overall survival (OS) in different groups divided according to the clinical factor, respectively. And the association between OS with multi clinical factors was examined using Cox regression analysis. Next, the risk factors for recurrence in patients with V1N1 were analyzed with univariate and multivariate logistic regression analyses, respectively.
Results: The cases in V0N0, V1N0, V0N1, and V1N1 groups were 91 (46.7%), 62 (31.8%), 9 (4.6%) and 33 (16.9%), respectively. The OS in the four groups was different (P < 0.001). The 1-, 3- and 5-year OS in V0N0 group was higher than that in V1N1 group, respectively (1-year OS: 93.4% vs 75.8%, 3-year OS: 53.8 % vs 24.2%, 5-year OS: 48.1% vs 10.5%). The OS in stage I-II for patients with V1N1 was significantly lower than that in the other groups (V0N0, V1N0, V0N1) (P < 0.001). The postoperative adjuvant chemotherapy was a significant impact factor of OS for ESCC patients with V1N1 (P = 0.004). Lymphatic invasion and LVI were significantly prognosis factors associated (P = 0.036, P = 0.030, respectively). The ulcerative type is a risk factor for V1N1 occurance (P = 0.040).
Conclusions: The LVI and PNI are important prognosis factors for ESCC patients. ESCC patients with simultaneous lymphangio vascular and perineural invasion (V1N1) showed worse OS than patients with either lymphangio vascular or perineural invasion alone (V1N0 or V0N1) or none (V0N0). In addition, adjuvant chemotherapy may prolong the OS for ESCC patients with V1N1.

Keywords:  Esophageal squamous cell carcinoma; Lymphangio vascular invasion; Overall survival; Perineural invasion; Prognosis

DOI:  https://doi.org/10.7717/peerj.12974
Zhonghua Wai Ke Za Zhi. 2022 Apr 01. 60(4): 357-363

[Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection].

J B Su, J W Zhang, C Chen, Y H Qiu, H Wu, T Q Song, Y He, X H Mao, W L Zhai, Z J Cheng, J D Li, S B Si, Z Q Cai, Z M Geng, Zhaohui Tang.

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion,perineural invasion,N stage,T stage,hepatic envelope invasion,adjuvant chemotherapy,tumor location,age,pathological differentiation,sex,alpha-fetoprotein and preoperative jaundice. A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase inthe probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.

DOI: https://doi.org/10.3760/cma.j.cn112139-20220110-00021
Am J Surg Pathol. 2022 Mar 08.

Clinicopathologic and Molecular Study of Hybrid Nerve Sheath Tumors Reveals Their Common Association With Fusions Involving VGLL3.

Hugo Nihous, Jessica Baud, Rihab Azmani, Audrey Michot, Raul Perret, Laetitia Mayeur, Gonzague de Pinieux, Serge Milin, Emilie Angot, Sébastien Duquenne, Damien Geneste, Carlo Lucchesi, Francois Le Loarer, Corinne Bouvier.

A subset of benign peripheral nerve sheath tumors are "hybrid" combining several lines of differentiation, most often schwannian and perineurial features. The pathogenesis of these tumors was poorly described until the recent discovery of recurrent VGLL3 rearrangements in hybrid schwannoma/perineuriomas, supporting the hypothesis that this entity represents a distinct subgroup of tumors and not only a morphologic variation of other peripheral nerve sheath tumors. Following this finding, we investigated 10 cases of hybrid peripheral nerve sheath tumors with immunohistochemistry, RNA sequencing, and array comparative genomic hybridization. By light microscopy, 7 tumors were hybrid schwannoma/perineurioma tumors, and 3 were hybrid schwannoma/neurofibroma. Most cases of hybrid schwannoma/perineuriomas displayed VGLL3 rearrangements fused in 5' either to CHD7 or CHD9 (n=6/7) and had simple diploid genetic profiles with few copy number alterations. Compared with a control group composed of 28 tumors associated with varied neural phenotypes, all VGLL3-fused tumors clustered together by transcriptomic analysis. In contrast, 1 case of hybrid schwannoma/perineurioma tumor harbored a CDH9-ZFHX3 fusion, a prominent perineurial component identified by immunohistochemistry and clustered with perineuriomas. No recurrent genetic alteration was seen in the 3 hybrid schwannoma/neurofibromas. To summarize, this study confirms and expands the recent findings on hybrid schwannoma/perineurioma, highlighting the predominance of VGLL3 fusions in these tumors.

DOI: https://doi.org/10.1097/PAS.0000000000001858
Cancers (Basel). 2022 Mar 01. pii: 1271. [Epub ahead of print]14(5):

Long-Term Feasibility of 13.56 MHz Modulated Electro-Hyperthermia-Based Preoperative Thermoradiochemotherapy in Locally Advanced Rectal Cancer.

Yohan Lee, Sunghyun Kim, Hyejung Cha, Jae Hun Han, Hyun Joon Choi, Eun Go, Sei Hwan You.

  We evaluated the effect of 13.56 MHz modulated electro-hyperthermia (mEHT) boost in neoadjuvant treatment for cT3-4- or cN-positive rectal cancer. Sixty patients who completed the mEHT feasibility trial (ClinicalTrials.gov Identifier: NCT02546596) were analyzed. Whole pelvis radiotherapy of 40 Gy, mEHT boost twice a week during radiotherapy, and surgical resection 6-8 weeks following radiotherapy were performed. The median age was 59. The median follow-up period was 58 (6-85) months. Total/near total tumor regression was observed in 20 patients (33.3%), including nine cases of complete response. T- and N-downstaging was identified in 40 (66.6%) and 53 (88.3%) patients, respectively. The 5-year overall and disease-free survival were 94.0% and 77.1%, respectively. mEHT energy of ≥3800 kJ potentially increased the overall survival (p = 0.039). The ypN-stage and perineural invasion were possible significant factors in disease-free (p = 0.003 and p = 0.005, respectively) and distant metastasis-free (p = 0.011 and p = 0.034, respectively) survival. Tumor regression, resection margin status, and other molecular genetic factors showed no correlation with survival. Although a limited analysis of a small number of patients, mEHT was feasible considering long-term survival. A relatively low dose irradiation (40 Gy) plus mEHT setting could ensure comparable clinical outcomes with possible mEHT-related prognostic features.

Keywords:  neoadjuvant chemoradiation; rectal cancer; regional hyperthermia; survival

DOI:  https://doi.org/10.3390/cancers14051271