bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–03–12
eleven papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. Perineural Invasion Predicts Unfavorable Prognosis in Patients With Invasive Breast Cancer.
  2. Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.
  3. Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.
  4. Psychoneuro-oncology: How Chronic Stress Grows Cancer.
  5. Chronic Adrenergic Stress and Generation of Myeloid-Derived Suppressor Cells: Implications for Cancer Immunotherapy in Dogs.
  6. Long-term results and prognostic factors after surgical treatment for gallbladder cancer.
  7. An investigation into tumor regression grade as a parameter for locally advanced rectal cancer and 5-year overall survival rate.
  8. Adrenal Schwannoma: Case Description and Diagnostic Pointers of a Rare Disease.
  9. Preoperative Psoas Muscle Thickness to Height Ratio Predicts Poor Survival After Resection of Biliary Tract Cancer.
  10. Prognostic analysis of curatively resected pancreatic cancer using harmonized positron emission tomography radiomic features.
  11. Adenoid Cystic Carcinoma (AdCC): A Clinical Survey of a Large Patient Cohort.
  1. Cancer Diagn Progn. 2023 Mar-Apr;3(2):3(2): 208-214
    Perineural Invasion Predicts Unfavorable Prognosis in Patients With Invasive Breast Cancer.
    Keiko Hosoya, Makoto Wakahara, Kohei Ikeda, Yoshihisa Umekita.
       BACKGROUND/AIM: Perineural invasion (PNI) is a poor prognostic factor in a variety of cancers. However, the frequency of PNI in invasive breast carcinoma varies among studies, and the prognostic significance of PNI remains unclear. Therefore, we aimed to explore the prognostic value of PNI in breast cancer patients.
    PATIENTS AND METHODS: The cohort included 191 consecutive female patients who underwent surgical resection of invasive carcinoma of no special type (NOS). The correlations between PNI and clinicopathological characteristics including prognosis were investigated.
    RESULTS: The frequency of PNI was 14.1% (27/191) and the PNI-positive status was significantly correlated with large pathological tumor size (p=0.005), lymph node metastasis (p=0.001), and lymphatic invasion (p=0.009). The log-rank test showed that PNI-positive patients had shorter distant metastasis-free survival (DMFS) (p=0.002) and disease-specific survival (DSS) (p<0.001). According to the multivariate analysis, PNI had a significant adverse effect on DMFS (p=0.037) and DSS (p=0.003).
    CONCLUSION: PNI could be used as an independent poor prognostic indicator in patients with invasive breast carcinoma.
    Keywords:  Perineural invasion; breast cancer; invasive carcinoma of no special type; prognostic factor
    DOI:  https://doi.org/10.21873/cdp.10203
  2. Cancers (Basel). 2023 Feb 21. pii: 1360. [Epub ahead of print]15(5):
    Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.
    Zirong Chen, Yan Fang, Weihong Jiang.
      Perineural invasion (PNI) as the fourth way for solid tumors metastasis and invasion has attracted a lot of attention, recent research reported a new point that PNI starts to include axon growth and possible nerve "invasion" to tumors as the component. More and more tumor-nerve crosstalk has been explored to explain the internal mechanism for tumor microenvironment (TME) of some types of tumors tends to observe nerve infiltration. As is well known, the interaction of tumor cells, peripheral blood vessels, extracellular matrix, other non-malignant cells, and signal molecules in TME plays a key role in the occurrence, development, and metastasis of cancer, as to the occurrence and development of PNI. We aim to summarize the current theories on the molecular mediators and pathogenesis of PNI, add the latest scientific research progress, and explore the use of single-cell spatial transcriptomics in this invasion way. A better understanding of PNI may help to understand tumor metastasis and recurrence and will be beneficial for improving staging strategies, new treatment methods, and even paradigm shifts in our treatment of patients.
    Keywords:  perineural invasion (PNI); single-cell spatial transcriptomics (sc-ST); tumor microenvironment (TME)
    DOI:  https://doi.org/10.3390/cancers15051360
  3. Ann Surg Oncol. 2023 Mar 10.
    Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.
    Jessica Limberg, Yeon J Lee-Saxton, Caitlin E Egan, AlAnoud AlAnazi, Imaani Easthausen, Dessislava Stefanova, Alexia Stamatiou, Toni Beninato, Rasa Zarnegar, Theresa Scognamiglio, Thomas J Fahey, Brendan M Finnerty.
       BACKGROUND: Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in papillary thyroid cancer (PTC) is incompletely characterized.
    METHODS: Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)-a surrogate marker of poor prognosis.
    RESULTS: In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%, p = 0.027), microscopic ETE (80.8% vs. 44.0%, p = 0.002), and a larger burden [median 5 (interquartile range [IQR] 2-13) vs. 2 (1-5), p = 0.010] and size [median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4), p = 0.008] of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE [odds ratio [OR] 4.9 (95% confidence interval [CI] 1.5-16.5), p = 0.008] compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months).
    CONCLUSIONS: PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.
    DOI:  https://doi.org/10.1245/s10434-023-13307-8
  4. Clin Dermatol. 2023 Mar 05. pii: S0738-081X(23)00035-4. [Epub ahead of print]
    Psychoneuro-oncology: How Chronic Stress Grows Cancer.
    Francisco Tausk.
      Chronic stress is an inextricable part of modern daily living; practically all human diseases are negatively affected by it, particularly cancer. Numerous studies have shown that stressors, depression, social isolation, and adversity correlate with a worse prognosis for patients with cancer, with increased symptoms, early metastasis, and a shortened life span. Prolonged or very intense adverse life episodes are perceived and assessed by the brain that translate into physiologic responses mediated through relays to the hypothalamus and locus coereleus. This triggers the activation of the hypothalamus-pituitary-adrenal axis (HPA) and the peripheral nervous system (PNS) with the secretion of glucocorticosteroids/epinephrine and nor-epinephrine (NE) . These hormones and neurotransmitters affect immune surveillance and the immune response to malignancies by skewing immunity from a Type 1 to a Type 2 response; this not only impedes the detection and killing of cancer cells but actually induces immune cells to facilitate cancer growth and systemic spread. This may be mediated by the engagement of norepinephrine to β adrenergic receptors, which can be partially reversed by the administration of β blockers.
    Keywords:  cancer; nerves; psychology; stress
    DOI:  https://doi.org/10.1016/j.clindermatol.2023.03.008
  5. Vet Comp Oncol. 2023 Mar 06.
    Chronic Adrenergic Stress and Generation of Myeloid-Derived Suppressor Cells: Implications for Cancer Immunotherapy in Dogs.
    Dylan T Ammons, Cameron R MacDonald, Lyndah Chow, Elizabeth A Repasky, Steven Dow.
      Recent studies have highlighted a key role played by the sympathetic nervous system (SNS) and adrenergic stress in mediating immune suppression associated with chronic inflammation in cancer and other diseases. The connection between chronic SNS activation, adrenergic stress, and immune suppression is linked in part to the ability of catecholamines to stimulate the bone marrow release and differentiation of myeloid-derived suppressor cells (MDSC). Rodent model studies have revealed an important role for β-adrenergic receptor signaling in suppression of cancer immunity in mice subjected to chronic stresses, including thermal stress. Importantly, therapeutic blockade of beta-adrenergic responses by drugs such as propranolol can partially reverse the generation and differentiation of MDSC, and partly restore tumor immunity. Clinical trials in both humans and dogs with cancer have demonstrated that propranolol blockade can improve responses to radiation therapy, cancer vaccines, and immune checkpoint inhibitors. Thus, the SNS stress response has become an important new target to relieve immune suppression in cancer and other chronic inflammatory conditions. This article is protected by copyright. All rights reserved.
    Keywords:  cytokines; immune cells; macrophage; norepinephrine; thermal stress
    DOI:  https://doi.org/10.1111/vco.12891
  6. Turk J Surg. 2022 Dec;38(4): 334-344
    Long-term results and prognostic factors after surgical treatment for gallbladder cancer.
    Mehmet Ali Uzun, Metin Tilki, Sevcan Alkan Kayaoğlu, Gülten Çiçek Okuyan, Zeynep Gamze Kılıçoğlu, Aylin Gönültaş.
       Objectives: Gallbladder cancer is relatively rare and traditionally regarded as having poor prognosis. There is controversy about the effects of clinicopathological features and different surgical techniques on prognosis. The aim of this study was to investigate the effects of clinicopathological characteristics of the patients with surgically treated gallbladder cancer on long-term survival.
    Material and Methods: We retrospectively analyzed the database of gallbladder cancer patients treated at our clinic between January 2003 and March 2021.
    Results: Of 101 evaluated cases, 37 were inoperable. Twelve patients were determined unresectable based on surgical findings. Resection with curative intent was performed in 52 patients. The one-, three-, five-, and 10-year survival rates were 68.9%, 51.9%, 43.6%, and 43.6%, respectively. Median survival was 36.6 months. On univariate analysis, poor prognostic factors were determined as advanced age; high carbohydrate antigen 19-9 and carcinoembryonic antigen levels; non-incidental diagnosis; intraoperative incidental diagnosis; jaundice; adjacent organ/structure resection; grade 3 tumors; lymphovascular invasion; and high T, N1 or N2, M1, and high AJCC stages. Sex, IVb/V segmentectomy instead of wedge resection, perineural invasion, tumor location, number of resected lymph nodes, and extended lymphadenectomy did not significantly affect overall survival. On multivariate analysis, only high AJCC stages, grade 3 tumors, high carcinoembryonic antigen levels, and advanced age were independent predictors of poor prognosis.
    Conclusion: Treatment planning and clinical decision-making for gallbladder cancer requires individualized prognostic assessment along with standard anatomical staging and other confirmed prognostic factors.
    Keywords:  Biliary tract surgical procedures; gallbladder neoplasm; prognostic factors; survival
    DOI:  https://doi.org/10.47717/turkjsurg.2022.5861
  7. Ann Coloproctol. 2023 Feb;39(1): 59-70
    An investigation into tumor regression grade as a parameter for locally advanced rectal cancer and 5-year overall survival rate.
    Supparerk Laohawiriyakamol, Wongsakorn Chaochankit, Worawit Wanichsuwan, Kanet Kanjanapradit, Teeranan Laohawiriyakamol.
       PURPOSE: The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by surgery. Several parameters are associated with patient survival in LARC. One of these parameters is tumor regression grade (TRG); however, the significance of TRG remains controversial. In this study, we aimed to examine the correlations of TRG with 5-year overall (OS) and relapse-free survival (RFS) and identify other factors that influence the survival rates in LARC after nCRT followed by surgery.
    METHODS: This retrospective study included 104 patients diagnosed with LARC who underwent nCRT followed by surgery at Songklanagarind Hospital from January 2010 to December 2015. All patients received fluoropyrimidine-based chemotherapy at a total dose of 45.0 to 50.4 Gy in 25 daily fractions. Tumor response was evaluated using the 5-tier Mandard TRG classification. TRG was categorized into good (TRG 1-2) and poor (TRG 3-5) responses.
    RESULTS: TRG (classified by either the 5-tier classification system or the 2-group classification system) was not correlated with 5-year OS or RFS. The 5-year OS rates were 80.0%, 54.5%, 80.8%, and 67.4% in patients with TRG 1, 2, 3, and 4, respectively (P=0.22). Poorly differentiated rectal cancer and systemic metastasis were associated with poor 5-year OS. Intraoperative tumor perforation, poor differentiation, and perineural invasion were correlated with inferior 5-year RFS.
    CONCLUSION: TRG was probably not associated with either 5-year OS or RFS; however, poor differentiation and systemic metastasis were strongly associated with poor 5-year OS.
    Keywords:  Chemoradiotherapy; Neoadjuvant therapy; Rectal cancer; Survival
    DOI:  https://doi.org/10.3393/ac.2021.01011.0144
  8. Cureus. 2023 Feb;15(2): e34485
    Adrenal Schwannoma: Case Description and Diagnostic Pointers of a Rare Disease.
    Shiraz A Mohd Ziauddin, Aditya P Sharma, Sudheer K Devana, Kim Vaiphei.
      Benign nerve sheath tumours such as schwannomas commonly involve the peripheral and cranial nerves. A schwannoma in the adrenal gland is a very rare occurrence, which arises from the adrenal medulla. Its most common presentation is a non-functional incidentaloma. It does not have any unique imaging characteristic distinguishing it from other adrenal masses; hence, its diagnosis is usually confirmed by final histopathology. In this report, we present two cases of an adrenal schwannoma for which we anticipated an unusual diagnosis, which was confirmed through adrenalectomy on histopathology.
    Keywords:  adrenal schwannoma; benign nerve sheath tumors; histopathology and immunohistochemistry; s-100; unilateral adrenalectomy
    DOI:  https://doi.org/10.7759/cureus.34485
  9. In Vivo. 2023 Mar-Apr;37(2):37(2): 879-886
    Preoperative Psoas Muscle Thickness to Height Ratio Predicts Poor Survival After Resection of Biliary Tract Cancer.
    Shinichi Ikuta, Tsukasa Aihara, Takayoshi Nakajima, Meidai Kasai, Naoki Yamanaka.
       BACKGROUND/AIM: Accumulating evidence suggests that muscle mass depletion (sarcopenia) has a negative impact on survival in several malignancies, including biliary tract cancer (BTC). Computed tomography (CT)-measured psoas muscle thickness to height ratio (PMTH) has been reported as a surrogate measure for muscle mass that does not require specialized equipment or software. The aim of this retrospective study was to investigate whether preoperative PMTH predicts oncological outcomes of patients undergoing surgical resection for BTC.
    PATIENTS AND METHODS: PMTH was assessed in 211 patients by analyzing axial CT images at the level of the umbilicus. The most predictive cutoff of PMTH was determined by survival classification and regression tree analysis. Propensity score-based inverse probability weighting (IPW) was used to balance characteristics between the low and high PMTH groups.
    RESULTS: Applying a PMTH cutoff of 17.5 mm/m, the low PMTH group comprised 114 patients (54%). Low PMTH was associated with female sex, non-obesity, CA19-9 elevation, and lymph node metastasis. After IPW adjustment, the low PMTH group had a significantly shorter disease-specific survival (p<0.001) and relapse-free survival (p<0.001) than the high PMTH group. IPW-adjusted regression analysis revealed that a low PMTH was independently associated with worse disease-specific survival (hazard ratio=2.98, p<0.001) and relapse-free survival (hazard ratio=2.49, p<0.001), in addition to other factors such as tumor differentiation, perineural invasion, and resection margin status.
    CONCLUSION: Preoperative PMTH may be a simple and feasible index of sarcopenia for predicting poor survival after resection of BTC.
    Keywords:  PMTH; Psoas muscle thickness; biliary tract cancer; sarcopenia
    DOI:  https://doi.org/10.21873/invivo.13156
  10. Eur J Hybrid Imaging. 2023 Mar 06. 7(1): 5
    Prognostic analysis of curatively resected pancreatic cancer using harmonized positron emission tomography radiomic features.
    Masao Watanabe, Ryo Ashida, Chisato Miyakoshi, Shigeki Arizono, Tsuyoshi Suga, Shotaro Kanao, Koji Kitamura, Takahisa Ogawa, Reiichi Ishikura.
       BACKGROUND: Texture features reflecting tumour heterogeneity enable us to investigate prognostic factors. The R package ComBat can harmonize the quantitative texture features among several positron emission tomography (PET) scanners. We aimed to identify prognostic factors among harmonized PET radiomic features and clinical information from pancreatic cancer patients who underwent curative surgery.
    METHODS: Fifty-eight patients underwent preoperative enhanced dynamic computed tomography (CT) scanning and fluorodeoxyglucose PET/CT using four PET scanners. Using LIFEx software, we measured PET radiomic parameters including texture features with higher order and harmonized these PET parameters. For progression-free survival (PFS) and overall survival (OS), we evaluated clinical information, including age, TNM stage, and neural invasion, and the harmonized PET radiomic features based on univariate Cox proportional hazard regression. Next, we analysed the prognostic indices by multivariate Cox proportional hazard regression (1) by using either significant (p < 0.05) or borderline significant (p = 0.05-0.10) indices in the univariate analysis (first multivariate analysis) or (2) by using the selected features with random forest algorithms (second multivariate analysis). Finally, we checked these multivariate results by log-rank test.
    RESULTS: Regarding the first multivariate analysis for PFS after univariate analysis, age was the significant prognostic factor (p = 0.020), and MTV and GLCM contrast were borderline significant (p = 0.051 and 0.075, respectively). Regarding the first multivariate analysis of OS, neural invasion, Shape sphericity and GLZLM LZLGE were significant (p = 0.019, 0.042 and 0.0076). In the second multivariate analysis, only MTV was significant (p = 0.046) for PFS, whereas GLZLM LZLGE was significant (p = 0.047), and Shape sphericity was borderline significant (p = 0.088) for OS. In the log-rank test, age, MTV and GLCM contrast were borderline significant for PFS (p = 0.08, 0.06 and 0.07, respectively), whereas neural invasion and Shape sphericity were significant (p = 0.03 and 0.04, respectively), and GLZLM LZLGE was borderline significant for OS (p = 0.08).
    CONCLUSIONS: Other than the clinical factors, MTV and GLCM contrast for PFS and Shape sphericity and GLZLM LZLGE for OS may be prognostic PET parameters. A prospective multicentre study with a larger sample size may be warranted.
    Keywords:  Complete surgery; FDG PET/CT; Harmonization; Overall survival; PET radiomics; Pancreatic cancer; Progression-free survival; Random forest
    DOI:  https://doi.org/10.1186/s41824-023-00163-8
  11. Cancers (Basel). 2023 Feb 27. pii: 1499. [Epub ahead of print]15(5):
    Adenoid Cystic Carcinoma (AdCC): A Clinical Survey of a Large Patient Cohort.
    Mark Zupancic, Anders Näsman, Anders Berglund, Tina Dalianis, Signe Friesland.
      Adenoid cystic carcinoma (AdCC), a rare heterogenous disease, presents diagnostic, prognostic, and therapeutic challenges. To obtain more knowledge, we conducted a retrospective study on a cohort of 155 patients diagnosed in 2000-2022 with AdCC of the head and neck in Stockholm and investigated several clinical parameters in correlation to treatment and prognosis in the 142/155 patients treated with curative intent. The strongest favourable prognostic factors were early disease stage (stage I and II) as compared to late disease (stage III and IV) and major salivary gland subsite as compared to other subsites, with the best prognosis in the parotid gland, irrespective of the stage of the disease. Notably, in contrast to some studies, a significant correlation to survival was not found for perineural invasion or radical surgery. However, similar to others, we confirmed that other common prognostic factors, e.g., smoking, age, and gender, did not correlate to survival and should not be used for prognostication of AdCC of the head and neck. To conclude, in AdCC early disease stage, major salivary gland subsite and multimodal treatment were the strongest favourable prognostic factors, while this was not the case for age, gender and smoking nor perineural invasion and radical surgery.
    Keywords:  adenoid cystic carcinoma; perineural invasion; prognostic factors; subsites; treatment
    DOI:  https://doi.org/10.3390/cancers15051499
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