bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2021‒12‒05
seven papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

  1. Dis Colon Rectum. 2021 Nov 24.
      BACKGROUND: Lymphovascular and perineural invasion are well-known negative prognostic indicators in rectal cancer but prior studies on their significance are not consistent.OBJECTIVE: This study assessed the prognostic value of lymphovascular and perineural invasion in rectal cancer patients who received preoperative chemoradiotherapy followed by curative resection.
    DESIGN: This is a retrospective analysis.
    SETTING: This study was performed at a tertiary cancer center.
    PATIENTS: Rectal cancer patients who underwent curative resection following preoperative chemoradiotherapy between January 2000 and December 2010.
    MAIN OUTCOME MEASURES: The primary outcomes were disease-free survival and overall survival. The survival rates were estimated using Kaplan-Meier analysis and group comparisons were conducted using a log-rank test.
    RESULTS: Of the 1,156 included patients, 109 (9.4%) presented with lymphovascular, and 137 (11.9%) with perineural invasion. Lymphovascular and perineural invasion were associated with T and N downstaging after preoperative chemoradiotherapy (p<0.001). In the ypN0 patients, the 5-year disease-free survival rates were 70.8% and 78.5% (p=0.150) for the lymphovascular invasion and absent groups, respectively. In the perineural invasion group, the 5-year disease-free survival rate was 59.0%, compared to 80.2% in the absent group (p=0.001). Among the ypN+ patients, the 5-year disease-free survival rates were 36.9% and 44.4% for the lymphovascular invasion and absent groups, respectively (p=0.211). The perineural invasion group showed poorer 5-year disease-free survival rate compared to the absent group (29.7% vs. 46.7%, p=0.011). By multivariable analyses, perineural invasion correlated with a poor disease-free survival (hazard ratio 1.412, 95% confidence interval 1.082-1.843; p=0.011) and also in ypN0 subgroup analysis (hazard ratio 1.717, 95% confidence interval 1.093-2.697; p=0.019).
    LIMITATIONS: This study was a retrospective study conducted at a single center.
    CONCLUSION: Perineural invasion is a reliable independent predictor of recurrence in rectal cancer patients treated with preoperative chemoradiotherapy. Patients with perineural invasion should be considered for closer surveillance even with ypN0 status. See Video Abstract at
  2. Crit Rev Oncol Hematol. 2021 Nov 26. pii: S1040-8428(21)00337-1. [Epub ahead of print] 103550
      INTRODUCTION: Although salvage surgery (SS) is considered the best curative choice in recurrent head and neck cancer, the identification of patients who can benefit the most from this treatment is challenging.METHODS: We systematically reviewed the prognostic role of pre- and post-surgery factors in patients undergoing SS for recurrent head and neck cancer (oral cavity, oropharynx, hypopharynx, and larynx).
    RESULTS: Twenty-five studies met the inclusion criteria out of 1280 screened citations. Pre-surgery factors significantly associated with worse overall survival were age>60 years, advanced initial stage, early recurrence, and regional recurrence; no heterogeneity between study emerged. Among post- surgery factors, worse survival emerged for positive surgical margins, extracapsular extension and perineural invasion.
    CONCLUSION: The identification of pre-surgery factors associated with poor outcomes may help the selection of the best candidate to SS; alternative treatments should be considered for high-risk patients. Post-surgery predictors of worse prognosis may guide clinicians in tailoring patients' surveillance.
    Keywords:  Head and neck cancer; Oral cancer; Overall survival; Progression-free survival; Salvage surgery
  3. J Clin Pathol. 2021 Dec 01. pii: jclinpath-2021-207957. [Epub ahead of print]
      AIMS AND METHODS: The prognostic role of tumour budding (TBd) and its interaction with the stromal microenvironment has gained a lot of attention recently, but remains unexplored in gall bladder cancer (GBC). We aimed to study the interrelationship of TBd by International Tumour Budding Consensus Conference scoring system, tumour-stroma ratio (TSR) and desmoplastic stromal reaction (DSR) with the conventional clinicopathological prognostic factors, mortality and overall survival (OS) in 96 patients of operated GBC.RESULTS: Higher age, high TNM stage, lymphovascular and perineural invasion, positive resection margins, higher TBd score, low TSR and immature DSR were significantly associated with worse OS. However, on multivariate analysis, only metastases, positive resection margins and TSR <50% proved to be independent prognostic factors. The TBd score of stroma-rich tumour group (6.40±4.69) was significantly higher than that of stroma-poor group (2.77±3.79, p≤0.001). The TBd score of immature and intermediate DSR groups was significantly higher than that of mature group (p≤0.001 and p=0.002, respectively). There was a strong interobserver agreement for TBd score, TSR and type of DSR (Cohen's Kappa=0.726 to 0.864, p≤0.001). Stroma-rich tumours were significantly associated with immature DSR and fibrotic DSR with high TSR (p≤0.001).
    CONCLUSION: A high TBd, low TSR and immature DSR were significantly associated with several high-risk clinicopathological parameters and poor OS in GBC. These novel, simple, reproducible and cost-effective parameters may be included in the routine reporting checklist for GBC as additional prognostic parameters that can substratify the high-risk patients.
    Keywords:  gallbladder neoplasms; pathology; stromal cells; surgical
  4. Front Oncol. 2021 ;11 784924
      Objective: Over many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral squamous cell carcinoma (OSCC) but also provided inconsistencies, making clinical application difficult. The 8th TNM staging system of OSCC has acknowledged the importance of some histopathological features, by incorporating depth of invasion (DOI) to T category and extranodal extension (ENE) to N category. The aim of this systematic review with meta-analysis is to determine the most clinically relevant histopathological features for risk assessment and treatment planning of OSCC and to elucidate gaps in the literature.Methods: A systematic review was conducted using PRISMA guidelines, and the eligibility criteria were based on population, exposure, comparison, outcome, and study type (PECOS). PubMed, Cochrane, Scopus, and Web of Science were searched for articles exploring the impact of histopathological features on OSCC outcomes with Cox multivariate analysis. Pooled data were subjected to an inverse variance method with random effects or fixed effect model, and the risk of bias was evaluated using quality in prognosis studies (QUIPS). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.
    Results: The study included 172 articles published from 1999 to 2021. Meta-analyses confirmed the prognostic potential of DOI, ENE, perineural invasion, lymphovascular invasion, and involvement of the surgical margins and brought promising results for the association of bone invasion, tumor thickness, and pattern of invasion with increased risk for poor survival. Although with a small number of studies, the results also revealed a clinical significance of tumor budding and tumor-stroma ratio on predicted survival of patients with OSCC. Most of the studies were considered with low or moderate risk of bias, and the certainty in evidence varied from very low to high.
    Conclusion: Our results confirm the potential prognostic usefulness of many histopathological features and highlight the promising results of others; however, further studies are advised to apply consistent designs, filling in the literature gaps to the pertinence of histopathological markers for OSCC prognosis.
    Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.
    Keywords:  histopathological markers; meta-analysis; oral cancer; prognosis; systematic review
  5. Oncoimmunology. 2021 ;10(1): 2004659
      Numerous studies have found that chronic stress could promote tumor progression and this may be related to inhibtion of immune system. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with immunosuppressive activity. MDSCs may represent a key link between chronic stress and tumor progression. However, the role of stress-induced MDSCs in breast cancer progression is unclear. The present study showed that pre-exposure of chronic stress could lead to MDSCs elevation and facilitated breast cancer metastasis in tumor-bearing mice. Adoptive transfer of MDSCs could significantly increase lung metastatic foci. In contrast, lung metastasis could be alleviated by depleting endogenous MDSCs with Gr-1 antibody. The concentration of norepinephrine in serum and the expression of tyrosine hydroxylase in bone marrow could be significantly elevated by chronic stress. Moreover, propranolol, an inhibitor of β-adrenergic signaling, could inhibit breast carcinoma metastasis and prevent the expansion of chronic stress-induced MDSCs. Further study revealed that the expressions of IL-6 and JAK/STAT3 signaling pathways were upregulated by chronic stress in mice, and this upregulation could be inhibited by propranolol. Blocking the IL-6 signal or inhibiting the activation of the JAK/STAT3 signaling pathway could reduce tumor growth and metastasis by attenuating the accumulation of MDSCs in vivo. Besides, propranolol inhibited the expression of IL-6 in supernatant of 4T1 cells induced by isoproterenol and reduced the proportion of inducible MDSCs in vitro. Taken together, these data indicated that chronic stress may accumulate MDSCs via activation of β-adrenergic signaling and IL-6/STAT3 pathway, thereby promoting breast carcinoma metastasis.
    Keywords:  Chronic stress; IL-6/STAT3; MDSCs
  6. Surgery. 2021 Nov 30. pii: S0039-6060(21)01107-7. [Epub ahead of print]
      BACKGROUND: Adjuvant systemic therapy is selectively considered for high-risk stage II colon cancer, but which patients benefit most from adjuvant systemic therapy is unclear.METHODS: Patients who underwent resection of stage II colon cancer were identified from the National Cancer Database (2010-2016). Risk-factors for decreased overall survival on multivariable analysis were used to establish a predictive risk-score model for all-cause mortality. After propensity matching within each risk group, 5-year overall survival was estimated based on receipt of adjuvant systemic therapy.
    RESULTS: Of the 15,241 patients evaluated, 2,857 (18.8%) received adjuvant systemic therapy. Risk factors for decreased overall survival included age >75 (hazard ratio 3.3, P < .001), male sex (hazard ratio 1.2, P < .001), White/Black race (hazard ratio 1.4, P = .020), preoperative carcinoembryonic antigen >3.5 ng/mL (hazard ratio 1.6, P < .001), T4a T-stage (hazard ratio 2.0, P < .001), T4b T-stage (hazard ratio 2.4, P < .001), lymphovascular invasion (hazard ratio 1.2, P = .003), perineural invasion (hazard ratio 1.3, P = .003), and non-R0 proximal/distal resection margins (hazard ratio 1.7, P < .001). An internally validated risk-score model using these factors was developed composed of low-risk (n = 8,489), moderate-risk (n = 4,623), and high-risk (n = 2,129) groups; within each group, 19.9%, 15.7%, and 20.8% of patients, respectively, received adjuvant systemic therapy. After propensity matching, adjuvant systemic therapy was not associated with improved 5-year overall survival for low-risk patients (89.8% vs 88.3%, P = .280), but was for moderate-risk (80.5% vs 70.8%, P < .001), and high-risk (65.2% vs 45.7%, P < .001) patients.
    CONCLUSION: A predictive risk-score model incorporating patient and tumor factors identifies a high-risk cohort of stage II colon cancer patients who may benefit from adjuvant systemic therapy, although the minority of these patients appear to be receiving treatment.
  7. BMJ Support Palliat Care. 2021 Dec 02. pii: bmjspcare-2021-003293. [Epub ahead of print]
      OBJECTIVES: Patients with cancer often suffer severe pain that is not relieved with systemic analgesics and requires further treatment options. This study aims to investigate whether peripheral nerve blocks are a feasible treatment option in patients with incurable cancer who suffer from severe pain.METHODS: All patients with advanced cancer who received a peripheral nerve block for the management of pain at the Tampere University Hospital between January 2015 and December 2018 were included in this retrospective study. The characteristics of the patients' features of the nerve blocks, opioid dosing (daily morphine equivalent) before and after the blocks, and patient-reported pain relief following peripheral block were assessed from the medical records.
    RESULTS: Sixteen of the 17 patients included in this study received pain relief through a nerve block. Daily opioid dose was decreased with the block in 12 (71%) patients with a median change in daily morphine equivalent of -20 mg (IQR: -180 to 9). One infection of the catheter and two other transient adverse events occurred, but none was serious or fatal.
    CONCLUSIONS: Peripheral nerve blocks seem safe and may provide considerable analgesia and decrease the need for opioids in patients with advanced cancer.
    Keywords:  cancer; pain