bims-netuvo 2023-10-01 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–10–01
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.
β-Adrenergic Signaling through ADRB1 Promotes CD8+ T-cell Exhaustion.
Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.
Malignant and Benign Peripheral Nerve Sheath Tumors in a Single Center: Value of Clinical and Ultrasound Features for the Diagnosis of Malignant Peripheral Nerve Sheath Tumor Compared With Magnetic Resonance Imaging.
Schwannoma of the Sciatic Nerve as a Cause of Extra-articular Knee Pain: Case Report and Literature Review.
Arterial Resection for Pancreatic Cancer: Feasibility and Current Standing in a High-Volume Center.
Circadian, hormonal, and sleep rhythms: effects on cancer progression implications for treatment.
Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

Hum Brain Mapp. 2023 Sep 26.

Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.

Poppy L A Schoenberg, Alexander K Song, Emily M Mohr, Baxter P Rogers, Todd E Peterson, Barbara A Murphy.

  Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of "sickness", that has knock-on effects to the blood-brain barrier, brain-spinal barrier, blood-cerebrospinal fluid barrier, neuro-axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof-of-concept study to link for the first time late non-CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO-binding PET tracer [11 C]-PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non-CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non-central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral-to-centralized inflammatory response in non-CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms.

Keywords:  cancer survivorship; diffusion tensor imaging; head and neck cancer; microglial activation; neuroinflammation; non-CNS cancer; positron emission tomography; systemic symptomatology

DOI:  https://doi.org/10.1002/hbm.26491
Cancer Discov. 2023 Sep 29. OF1

β-Adrenergic Signaling through ADRB1 Promotes CD8+ T-cell Exhaustion.

The β1-adrenergic receptor is a T-cell immune checkpoint in chronic infection and in cancer.

DOI: https://doi.org/10.1158/2159-8290.CD-RW2023-154
J Neurooncol. 2023 Sep 27.

Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.

Archis R Bhandarkar, Shaan Bhandarkar, Dusica Babovic-Vuksanovic, Ian F Parney, Robert J Spinner.

   PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that arise from peripheral nerves and are the leading cause of mortality in Neurofibromatosis Type 1 (NF1). In this study, we characterized whether transcriptomic signatures of T-cell dysfunction (TCD) and exclusion (TCE) that inversely correlate with response to immune checkpoint blockade (ICB) immunotherapy exist in MPNSTs.
METHODS: MPNST transcriptomes were pooled from Gene Expression Omnibus (GEO). For each sample, a tumor immune dysfunction and exclusion (TIDE) score, TCD and TCE subscores, and cytotoxic T-cell(CTL) level were calculated. In the TIDE predictive algorithm, tumors are predicted to have an ICB response if they are either immunologically hot (CTL-high) without TCD or immunologically cold (CTL-low) without TCE. TIDE scores greater than zero correspond with ICB nonresponse.
RESULTS: 73 MPNST samples met inclusion criteria, including 50 NF1-associated MPNSTs (68.5%). The average TIDE score was + 0.41 (SD = 1.16) with 22 (30.1%) predicted ICB responders. 11 samples were CTL-high (15.1%) with an average TCD score of + 0.99 (SD = 0.63). Among 62 CTL-low tumors, 21 were predicted to have ICB response with an average TCE score of + 0.31(SD = 1.20). Age(p = 0.18), sex(p = 0.41), NF1 diagnosis (p = 0.17), and PRC2 loss(p = 0.29) were not associated with ICB responder status.
CONCLUSIONS: Transcriptomic analysis of TCD and TCE signatures in MPNST samples reveals that a select subset of patients with MPNSTs may benefit from ICB immunotherapy.

Keywords:  Immune checkpoint inhibitor; Immune dysfunction; Immunotherapy; Malignant peripheral nerve sheath tumor; Nerve sheath tumor

DOI:  https://doi.org/10.1007/s11060-023-04467-4
J Ultrasound Med. 2023 Sep 29.

Malignant and Benign Peripheral Nerve Sheath Tumors in a Single Center: Value of Clinical and Ultrasound Features for the Diagnosis of Malignant Peripheral Nerve Sheath Tumor Compared With Magnetic Resonance Imaging.

Zhenzhen Jin, Chao Wang, Dandan Wang, Xintong Li, Wen Guo, Tao Chen.

   OBJECTIVES: This study aimed to investigate the combined use of ultrasonography and clinical features for the differentiation of malignant peripheral nerve sheath tumors (MPNST) from benign peripheral nerve sheath tumors (BPNST) and to compare the efficacy of ultrasonography with that of magnetic resonance imaging (MRI).
METHODS: This retrospective study included 28 MPNSTs and a control group of 57 BPNSTs. All patients underwent an ultrasound scan using the Logiq E9 (GE Health Care, Milwaukee, WI) or EPIQ7 equipment (Philips Medical System, Bothell, WA). A 3.0-T MRI machine (Ingenia; Philips Healthcare, Best, the Netherlands) was used for scanning, and conventional MRI was performed on different regions based on the patient's clinical situation. The following variables were evaluated: palpable mass, pain, nerve symptoms, maximum diameter, location, shape, boundary, encapsulation, echogenicity, echo homogeneity, presence of a cystic component, calcification, target sign, posterior echo, and intertumoral vascularity of the tumors. The diagnostic efficacy of ultrasonography and clinical factors was compared with that of MRI. Independent factors for predicting MPNST versus BPNST were also assessed.
RESULTS: The parameters of location, shape, boundary, encapsulation, and vascularity were significantly different between MPNSTs and BPNSTs. Multiple logistic regression analysis showed that shape, boundary, and vascularity were independent predictors of MPNSTs. The sensitivity, specificity, and Youden index of the three clinical and ultrasound factors (shape, boundary, and vascularity) were 0.89, 0.81, and 0.69, respectively, whereas those of MRI were 0.71, 0.89, and 0.61, respectively. No significant differences in the area under the curve (AUC) of the three combined clinical and ultrasound factors and those of MRI were found (P > .05).
CONCLUSIONS: MRI was useful in the differential diagnosis between MPNSTs and BPNSTs. However, the combination of clinical and ultrasound diagnoses can achieve the same effect as MRI, including shape, boundary, and vasculature.

Keywords:  BPNST; MPNST; MRI; malignant; ultrasound

DOI:  https://doi.org/10.1002/jum.16330
J Orthop Case Rep. 2023 Sep;13(9): 93-98

Schwannoma of the Sciatic Nerve as a Cause of Extra-articular Knee Pain: Case Report and Literature Review.

Collen Sandile Nkosi, Nyiko Zakaria Chauke.

   Introduction: Schwannomas are rare benign tumors of the nerve sheath that originate from the Schwann cells of the peripheral nerve and have a broad anatomic distribution that includes superficial tissues, deep tissues, including the central nervous system, and the gastrointestinal system.
Case Report: A 60-year-old male presented with left knee pain for 5 years. This pain was associated with paresthesia, night pain unresponsive to analgesia, on the left foot intermittent pins and needles sensation. Schwannoma lesion was excised, histology confirmed the diagnosis, and the patient's symptoms improved.
Conclusion: Schwannoma around the knee is a rare or atypical cause of the non-arthritic pain and should be considered in the differential diagnosis of non-arthritic and extra-articular causes of knee pain with neurological deficit of the foot in an adult population.

Keywords:  Schwannoma; benign tumor; knee pain; sciatic nerve

DOI:  https://doi.org/10.13107/jocr.2023.v13.i09.3890
Ann Surg Open. 2023 Sep;4(3): e302

Arterial Resection for Pancreatic Cancer: Feasibility and Current Standing in a High-Volume Center.

Lei Ren, Carsten Jäger, Stephan Schorn, Ilaria Pergolini, Rüdiger Göß, Okan Safak, Maximilian Kießler, Marc E Martignoni, Alexander R Novotny, Helmut Friess, Güralp O Ceyhan, Ihsan Ekin Demir.

   Background: Arterial resection (AR) during pancreatectomy for curative R0 resection of pancreatic ductal adenocarcinoma (PDAC) remains a controversial procedure with high morbidity.
Objective: To investigate the feasibility and oncological outcomes of pancreatectomy combined with AR at a high-volume center for pancreatic surgery.
Methods: We retrospectively analyzed our experience in PDAC patients, who underwent pancreatic resection with AR and/or venous resection (VR) between 2007 and 2021.
Results: In total 259 PDAC patients with borderline resectable (n = 138) or locally advanced (n = 121) PDAC underwent vascular resection during tumor resection. From these, 23 patients had AR (n = 4 due to intraoperative injury, n = 19 due to suspected arterial infiltration). However, 12 out of 23 patients (52.2%) underwent simultaneous VR including 1 case with intraoperative arterial injury. In comparison, 11 patients (47.8%) underwent AR only including 3 intraoperative arterial injury patients. Although the operation time and bleeding rate of patients with AR were respectively longer and higher than in VR, no significant difference was detected in postoperative complications between VR and AR (P = 0.11). The final histopathological findings of PDAC patients were similar, including M stage, regional lymph node metastases, and R0 margin resection. The mortality of the entire cohort was 6.2% (16/259), with a tendency to increase mortality in the AR cohort, yet without statistical significance (VR: 5% vs AR: 21.1%; P = 0.05). Although 19 (82.6%) patients had PDAC in the final histopathology, only 6 were confirmed to have infiltrated arteria. The microscopic distribution of PDAC in these infiltrated arterial walls on hematoxylin-eosin staining was classified into 3 patterns. Strikingly, the perivascular nerves frequently exhibited perineural invasion.
Conclusions: AR can be performed in high-volume centers for pancreatic surgery with an acceptable morbidity, which is comparable to that of VR. However, the likelihood of arterial infiltration seems to be rather overestimated, and as such, AR might be avoidable or replaced by less invasive techniques such as divestment during PDAC surgery.

Keywords:  R0 resection; arterial resection; pancreatic cancer; venous resection

DOI:  https://doi.org/10.1097/AS9.0000000000000302
Front Oncol. 2023 ;13 1269378

Circadian, hormonal, and sleep rhythms: effects on cancer progression implications for treatment.

Annemarie D Jagielo, Catherine Benedict, David Spiegel.

  Circadian, hormonal, and sleep rhythm disruptions are commonly experienced concerns among cancer patients throughout the cancer care continuum. This review aims to summarize the existing literature on circadian, hormonal, and sleep rhythms in the oncological population, focusing on circadian disruption and physiological and psychological abnormalities, disease progression, and chronomodulated treatment approaches. The findings demonstrate that subjectively and objectively measured circadian rhythm disruption is associated with adverse mental health and disease outcomes in patients with cancer. Chronomodulated chemotherapy, light therapy, cognitive behavioral therapy for insomnia, and physical activity have shown evidence of effectiveness in improving sleep, and occasionally, disease outcomes.

Keywords:  cancer; chronotherapeutics; circadian rhythms; cortisol; sleep disturbance

DOI:  https://doi.org/10.3389/fonc.2023.1269378
Skeletal Radiol. 2023 Sep 27.

Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

Makoto Emori, Hiroyuki Tsuchie, Hiroyuki Takashima, Atsushi Teramoto, Yasutaka Murahashi, Yoshinori Imura, Hidetatsu Outani, Sho Nakai, Satoshi Takenaka, Ryosuke Hirota, Naoya Nakahashi, Junya Shimizu, Kazuyuki Murase, Akira Takasawa, Hiroyuki Nagasawa, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Seiji Okada, Naohisa Miyakoshi, Toshihiko Yamashita.

   BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST).
METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model.
RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS.
CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

Keywords:  Coefficient of variation; MRI; Malignant peripheral nerve sheath tumor; Prognosis

DOI:  https://doi.org/10.1007/s00256-023-04457-7