bims-netuvo 2021-12-12 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2021–12–12
seven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Molecular and Cellular Mechanisms of Perineural Invasion in Oral Squamous Cell Carcinoma: Potential Targets for Therapeutic Intervention.
Development and Validation of an MRI-Based Nomogram Model for Predicting Disease-Free Survival in Locally Advanced Rectal Cancer Treated With Neoadjuvant Radiotherapy.
Identifying BWH stage T2a cutaneous squamous cell carcinoma at risk for poor outcomes.
Distant metastasis in oral squamous cell carcinoma: Does the neutrophil-to-lymphocyte ratio act as a surrogate of the host immune status?
Early and late recurrences in lymph node-negative gastric cancer: a retrospective cohort study.
Computational Modeling of an Endovascular Peripheral Nerve Interface.
Robust, wireless gastric optogenetic implants for the study of peripheral pathways and applications in obesity.

Cancers (Basel). 2021 Nov 29. pii: 6011. [Epub ahead of print]13(23):

Molecular and Cellular Mechanisms of Perineural Invasion in Oral Squamous Cell Carcinoma: Potential Targets for Therapeutic Intervention.

Carly I Misztal, Carlos Green, Christine Mei, Rita Bhatia, Jaylou M Velez Torres, Brandon Kamrava, Seo Moon, Elizabeth Nicolli, Donald Weed, Zoukaa Sargi, Christine T Dinh.

  The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased survival and an increased rate of locoregional recurrence. In the classical theory of PNI, cancer was believed to invade nerves directly through the path of least resistance in the perineural space; however, more recent evidence suggests that PNI requires reciprocal signaling interactions between tumor cells and nerve components, particularly Schwann cells. Specifically, head and neck SCC can express neurotrophins and neurotrophin receptors that may contribute to cancer migration towards nerves, PNI, and neuritogenesis towards cancer. Through reciprocal signaling, recent studies also suggest that Schwann cells may play an important role in promoting PNI by migrating toward cancer cells, intercalating, and dispersing cancer, and facilitating cancer migration toward nerves. The interactions of neurotrophins with their high affinity receptors is a new area of interest in the development of pharmaceutical therapies for many types of cancer. In this comprehensive review, we discuss diagnosis and treatment of oral cavity SCC, how PNI affects locoregional recurrence and survival, and the impact of adjuvant therapies on tumors with PNI. We also describe the molecular and cellular mechanisms associated with PNI, including the expression of neurotrophins and their receptors, and highlight potential targets for therapeutic intervention for PNI in oral SCC.

Keywords:  PNI; Schwann cells; chemotherapy; nerve; neurotrophin; oral cavity; perineural invasion; radiation; squamous cell carcinoma

DOI:  https://doi.org/10.3390/cancers13236011
Front Oncol. 2021 ;11 784156

Development and Validation of an MRI-Based Nomogram Model for Predicting Disease-Free Survival in Locally Advanced Rectal Cancer Treated With Neoadjuvant Radiotherapy.

Silin Chen, Yuan Tang, Ning Li, Jun Jiang, Liming Jiang, Bo Chen, Hui Fang, Shunan Qi, Jing Hao, Ningning Lu, Shulian Wang, Yongwen Song, Yueping Liu, Yexiong Li, Jing Jin.

   Objectives: To develop a prognostic prediction MRI-based nomogram model for locally advanced rectal cancer (LARC) treated with neoadjuvant therapy.
Methods: This was a retrospective analysis of 233 LARC (MRI-T stage 3-4 (mrT) and/or MRI-N stage 1-2 (mrN), M0) patients who had undergone neoadjuvant radiotherapy and total mesorectal excision (TME) surgery with baseline MRI and operative pathology assessments at our institution from March 2015 to March 2018. The patients were sequentially allocated to training and validation cohorts at a ratio of 4:3 based on the image examination date. A nomogram model was developed based on the univariate logistic regression analysis and multivariable Cox regression analysis results of the training cohort for disease-free survival (DFS). To evaluate the clinical usefulness of the nomogram, Harrell's concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were conducted in both cohorts.
Results: The median follow-up times were 43.2 months (13.3-61.3 months) and 32.0 months (12.3-39.5 months) in the training and validation cohorts. Multivariate Cox regression analysis identified MRI-detected extramural vascular invasion (mrEMVI), pathological T stage (ypT) and perineural invasion (PNI) as independent predictors. Lymphovascular invasion (LVI) (which almost reached statistical significance in multivariate regression analysis) and three other independent predictors were included in the nomogram model. The nomogram showed the best predictive ability for DFS (C-index: 0.769 (training cohort) and 0.776 (validation cohort)). It had a good 3-year DFS predictive capacity [area under the curve, AUC=0.843 (training cohort) and 0.771 (validation cohort)]. DCA revealed that the use of the nomogram model was associated with benefits for the prediction of 3-year DFS in both cohorts.
Conclusion: We developed and validated a novel nomogram model based on MRI factors and pathological factors for predicting DFS in LARC treated with neoadjuvant therapy. This model has good predictive value for prognosis, which could improve the risk stratification and individual treatment of LARC patients.

Keywords:  magnetic resonance imaging; neoadjuvant therapy; nomograms; prognosis; rectal neoplasms

DOI:  https://doi.org/10.3389/fonc.2021.784156
J Am Acad Dermatol. 2021 Dec 02. pii: S0190-9622(21)02918-2. [Epub ahead of print]

Identifying BWH stage T2a cutaneous squamous cell carcinoma at risk for poor outcomes.

Neha Gupta, Rachel E Weitzman, Fadi Murad, Shlomo A Koyfman, Timothy D Smile, Michael S Chang, Jacqueline M Maher, Chrysalyne D Schmults, Allison T Vidimos, Emily S Ruiz.

   BACKGROUND: Most cutaneous squamous cell carcinoma (CSCC) poor outcomes occur in high-stage tumors. However, 26% of nodal metastases (NM) and 8% of disease-specific deaths (DSD) develop in Brigham and Women's Hospital (BWH) T2a tumors.
OBJECTIVE: To determine risk factors associated with poor outcomes (NM, distant metastases, DSD) in BWH T2a CSCC.
METHODS: 17-year retrospective multi-institutional cohort study of primary CSCC BWH T2a tumors. A predictive model based on tumor characteristics was developed to identify those at higher risk of poor outcomes.
RESULTS: Presence of 1 major (primary tumor diameter ≥40mm, invasion depth beyond subcutaneous fat, poor differentiation, and large caliber perineural invasion (PNI)) and ≥1 minor criteria (invasion depth in subcutaneous fat, moderate differentiation, small caliber PNI and lymphovascular invasion) was most predictive of developing poor outcomes (AUC 0.53, C-statistic 0.60). This model has a sensitivity of 7.7%, specificity of 97.4%, and a positive and negative predictive value of 33.3% and 86.1%, respectively. The five-year cumulative incidence of poor outcomes in these tumors is 8.0% (95% CI:5.1-13.7) compared to 2.8% (95% CI:1.9-4.1) in other T2a tumors (SHR 3.0, 95% CI:1.5-5.8).
LIMITATIONS: Multi-institutional cohort study not externally validated.
CONCLUSIONS: BWH T2a-high CSCCs have an 8% chance of developing poor outcomes.

Keywords:  cutaneous squamous cell carcinoma; disease-specific death; distant metastasis; nodal metastasis

DOI:  https://doi.org/10.1016/j.jaad.2021.11.046
Oral Oncol. 2021 Dec 01. pii: S1368-8375(21)00748-X. [Epub ahead of print]124 105641

Distant metastasis in oral squamous cell carcinoma: Does the neutrophil-to-lymphocyte ratio act as a surrogate of the host immune status?

Daniella Karassawa Zanoni, Cristina Valero, Marlena R McGill, Pablo H Montero, Jatin P Shah, Richard J Wong, Ian Ganly, Snehal G Patel.

   OBJECTIVES: Distant metastasis (DM) is an important prognostic factor for oral squamous cell carcinoma (OSCC). The aim of this study is to evaluate the influence of host and tumor factors in development of DM.
MATERIALS AND METHODS: After IRB approval, 1369 patients with OSCC undergoing primary surgery were eligible for the study. The primary endpoint was the development of distant metastasis (DM). Patients were pathologically staged according to the American Joint Committee on Cancer, 8th Edition. Pre-operative peripheral blood counts were used to calculate neutrophil-to-lymphocyte ratio (NLR).
RESULTS: Median follow-up was 39 months (range 1-221). DM were identified in 126 patients during follow-up. When analyzed as a time-dependent covariate, neck recurrence (NR) was a significant predictor of DM (HR 16.35, 95% CI: 11.39-23.47, p < 0.001). NLR, margin status, vascular invasion, perineural invasion (PNI), grade, pT, number of metastatic lymph nodes, level IV involvement, and extra nodal-extension (ENE) were also significant. In multivariable analysis, NLR, margins, PNI, number of metastatic lymph nodes, and ENE maintained independent predictive capacity. Patients with NLR ≥ 5.7 were 3 times more likely to develop DM compared to NLR ≤ 2.9 (95% CI: 1.74-5.59, p < 0.001), patients with ≥ 5 metastatic lymph nodes were 2 times more likely to develop DM (95% CI: 1.18-3.60, p = 0.011), and those with ENE were 4 times more likely (95% CI: 2.67-8.20, p < 0.001) when compared to pNx/pN0 patients.
CONCLUSIONS: NLR, number of metastatic lymph nodes, and ENE were the strongest independent predictors of DM in OSCC treated with primary surgery and appropriate adjuvant therapy.

Keywords:  Distant metastases; Head and neck cancer; Neutrophil-to-lymphocyte ratio; Oral cancer; Squamous cell carcinoma

DOI:  https://doi.org/10.1016/j.oraloncology.2021.105641
Ann Saudi Med. 2021 Nov-Dec;41(6):41(6): 336-349

Early and late recurrences in lymph node-negative gastric cancer: a retrospective cohort study.

Jian-Wei Sun, Dao-Li Liu, Jia-Xian Chen, Li-Zhen Lin, Lv-Ping Zhuang, Xian-Hai Hou.

BACKGROUND: Predictors of recurrence in patients with lymph node-negative gastric cancer (GC) who have undergone curative resection have been widely investigated, but not the effects of predictors on timing of recurrence.
OBJECTIVE: Determine the factors associated with early and late recurrence in patients with node-negative GC.
DESIGN: Retrospective cohort.
SETTING: Academic tertiary care center.
PATIENTS AND METHODS: The study included patients with node-negative GC after curative resection between 2008 and 2018 at two institutions. Early and late recurrences were determined using a minimum P value approach to evaluate the optimal cutoff for recurrence-free survival (RFS). A competing risk model and landmark analysis were used to analyze factors associated with early and late recurrences.
MAIN OUTCOME MEASURES: Recurrence-free survival and factors associated with survival.
SAMPLE SIZE: 606.
RESULTS: After a median follow-up of 70 months, 50 (8.3%) patients experienced recurrent disease. The optimal length of RFS for distinguishing between early (n=26) and late recurrence (n=24) was 24 months (P=.0013). The median RFS in the early and late recurrence groups was 11 and 32 months, respectively. Diffuse tumors (hazard ratio 3.358, P=.014), advanced T stage (HR 8.804, P=.003), perineural invasion (HR 10.955, P<.001), and anemia (HR 2.351, P=.018) were independent predictors of early recurrence. Mixed tumor location (HR 5.586, P=.002), advanced T stage (HR 5.066, P<.001), lymphovascular invasion (HR 5.902, P<.001), and elevated CA19-9 levels (HR 5.227, P<.001) were independent predictors of late recurrence. Similar results were obtained in the landmark analysis.
CONCLUSIONS: Individualized therapeutic and follow-up strategies should be considered in future studies because of distinct patterns in predictors of early and late recurrence.
LIMITATIONS: Retrospective design, small sample size.
CONFLICT OF INTEREST: None.

DOI: https://doi.org/10.5144/0256-4947.2021.336
Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021 5966-5969

Computational Modeling of an Endovascular Peripheral Nerve Interface.

JingYang Liu, David B Grayden, Janet R Keast, Sam E John.

Implantable neuromodulation devices that interface with the peripheral nervous system are a promising approach to restore functions lost to nerve damage. Existing nerve stimulation electrodes require direct contact with the target nerve and are associated with mechanical nerve damage and fibrous tissue encapsulation. Endovascularly delivered electrode arrays may provide a less invasive solution. Using a hybrid tissue conductor-neuron model and computational simulations, this study demonstrates the feasibility of delivering electrical stimulation of a peripheral nerve from a blood vessel in the vicinity of the target and predicts that the stimulation intensity required strongly depends on nerve-vessel distance and relative orientation, which are important factors to consider when screening candidate blood vessels for electrode implantation.

DOI: https://doi.org/10.1109/EMBC46164.2021.9630085
Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021 5742-5746

Robust, wireless gastric optogenetic implants for the study of peripheral pathways and applications in obesity.

Woo Seok Kim, Sungcheol Hong, Sung Il Park.

Optogenetics has the potential to transform the study of organ functions in the peripheral nervous system via relatively easy access to the nerves and a direct link between the brain and organ systems. Implementation typically requires a static skeletal feature for the securement of a fiber. Unfortunately, the soft nature of peripheral nervous systems makes the wired fiber-optic approach less ideal for the study of the peripheral nervous system. Existing wireless approaches could bypass some constraints associated with optical fibers and thereby offer organ specificity. However, they suffer from durability loss due to considerable biological strains and unable to perform longitudinal experiments. Here, we propose a new class of wireless gastric optogenetic implant for identifying signaling pathways, in particular viscerosensory pathways, that can regulate food intake to treat obesity. Robust, wireless gastric optogenetic implants with a tubing-assisted U-shaped tether directly interface with nerve endings in the stomach with chronic stability in operation (> 100 kilocycles) and allows for optogenetic stimulations of vagus nerves in a freely behaving animal. We demonstrated utilities of the proposed wireless device in in vivo experiments. Results suggest the potential for identifying interventions for the treatment of obesity.Clinical Relevance - Identification of the roles of subpopulations in viscerosensory pathways would provide the platform for the development of better therapeutics for the treatment of obesity.

DOI: https://doi.org/10.1109/EMBC46164.2021.9629753