bims-netuvo 2023-07-23 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–07–23
ten papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Targeting the Nerve-Cancer Circuit.
Is vagotomy necessary in palliative surgery for incurable advanced gastric cancer?: a retrospective case-control study.
The acid-sensing nociceptor TRPV1 controls breast cancer progression in bone via regulating HGF secretion from sensory neurons.
Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study.
Cancer cell employs a microenvironmental neural signal trans-activating nucleus-mitochondria coordination to acquire stemness.
Rare giant schwannoma of superficial peroneal nerve on the dorsum of foot.
7T for clinical imaging of benign peripheral nerve tumors: preliminary results.
Prognostic Predicting Model of Pancreatic Body Tail Carcinoma Using Clinical and CT Radiomic Data.
Advancements in therapeutic approaches for malignant peripheral nerve sheath tumor.
Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

Cancer Res. 2023 Jul 20. OF1-OF3

Targeting the Nerve-Cancer Circuit.

Yi Ye, Tongxin Xie, Moran Amit.

The tumor microenvironment is innervated by sensory, sympathetic, and parasympathetic nerves that actively stimulate cancer growth and dissemination. The cross-talk among the peripheral nerves, cancer cells, and stromal cells is mediated by a diverse set of bioactive ligands and their corresponding receptors. Dissecting the specific neuronal subtypes and molecular signals that drive cancer-nerve interaction holds the hope of developing targeted therapies for cancer. A recent study by Restaino and colleagues demonstrated that regardless of tumor type, origin, or anatomic location, tumors are densely innervated, predominantly by transient receptor potential cation channel subfamily V member 1 positive (TRPV1+) sensory fibers. The intratumoral fibers likely have functional connectivity and contribute to increased electrical activity in the tumor bed. Importantly, the neuropeptide substance P produced by intratumoral fibers stimulates its neurokinin 1 receptor (NK1R) expressed on tumor cells to drive tumor proliferation and migration. The findings raised the intriguing possibility of a generalizable molecular pathway that mediates cancer-nerve interaction that can be targeted to inhibit tumor growth and metastasis across different tumor types.

DOI: https://doi.org/10.1158/0008-5472.CAN-23-1754
World J Surg Oncol. 2023 Jul 21. 21(1): 213

Is vagotomy necessary in palliative surgery for incurable advanced gastric cancer?: a retrospective case-control study.

Yong-Eun Park.

   BACKGROUND: The interplay between the nervous system and cancer plays an important role in the initiation and progression of gastric cancer. Few studies have presented evidence that the sympathetic nervous system inhibits the occurrence and development of gastric cancer while the parasympathetic nervous system promotes the growth of gastric cancer. To investigate the effect of vagotomy, which is the resection of a parasympathetic nerve innervating the stomach, on the progression of gastric cancer, a retrospective study was conducted comparing the prognosis of simple palliative gastrojejunostomy (PGJ) and palliative gastrojejunostomy with vagotomy (PGJV).
METHODS: From January 01, 2000, to December 31, 2021, the medical records of patients who underwent PGJ or PGJV because of gastric outlet obstruction due to incurable advanced gastric cancer at the Yeungnam University Medical Center were retrospectively reviewed. Patients were divided into two groups: locally unresectable gastric cancer (LUGC) or gastric cancer with distant metastasis (GCDM), according to the reason for gastrojejunostomy, and factors affecting overall survival (OS) were analyzed.
RESULTS: There was no significant difference in surgical outcomes and postoperative complications between the patients with PGJV and patients with PGJ. In univariate analysis, vagotomy was not a significant factor for OS in the GCDM group (HR 1.14, CI 0.67-1.94, p value 0.642), while vagotomy was a significant factor for OS in the LUGC group (HR 0.38, CI 0.15-0.98, p value 0.045). In multivariate analysis, when vagotomy is performed together with PGJ for LUGC, the OS can be significantly extended (HR 0.25, CI 0.09-0.068, p value 0.007).
CONCLUSIONS: When PGJ for LUGC was performed with vagotomy, additional survival benefits could be achieved with low complication risk. However, to confirm the effect of vagotomy on the growth of gastric cancer, further prospective studies using large sample sizes are essential.

Keywords:  Gastric cancer; Palliative gastrojejunostomy; Vagotomy

DOI:  https://doi.org/10.1186/s12957-023-03111-9
Res Sq. 2023 Jul 05. pii: rs.3.rs-3105966. [Epub ahead of print]

The acid-sensing nociceptor TRPV1 controls breast cancer progression in bone via regulating HGF secretion from sensory neurons.

Tatsuo Okui, Masahiro Hiasa, Kenji Hata, G David Roodman, Masako Nakanishi, Toshiyuki Yoneda.

Cancers showing excessive innervation of sensory neurons (SN) in their microenvironments are associated with poor outcomes due to promoted growth, increased tumor recurrence, metastasis, and cancer pain, suggesting SNs play a regulatory role in cancer aggressiveness. Using a preclinical model in which mouse 4T1 breast cancer (BC) cells were injected into the bone marrow of tibiae, we found 4T1 BC cells aggressively colonized bone with bone destruction and subsequently spread to the lung. Of note, 4T1 BC colonization induced the acidic tumor microenvironment in bone in which SNs showed increased innervation and excitation with elevated expression of the acid-sensing nociceptor transient receptor potential vanilloid-1 (TRPV1), eliciting bone pain (BP) assessed by mechanical hypersensitivity. Further, these excited SNs produced increased hepatocyte growth factor (HGF). Importantly, the administration of synthetic and natural TRPV1 antagonists and genetic deletion of TRPV1 decreased HGF production in SNs and inhibited 4T1 BC colonization in bone, pulmonary metastasis from bone, and BP induction. Our results suggest the TRPV1 of SNs promotes BC colonization in bone and lung metastasis via up-regulating HGF production in SNs. The SN TRPV1 may be a novel therapeutic target for BC growing in the acidic bone microenvironment and for BP.

DOI: https://doi.org/10.21203/rs.3.rs-3105966/v1
BMC Cancer. 2023 Jul 18. 23(1): 675

Combining perineural invasion with staging improve the prognostic accuracy in colorectal cancer: a retrospective cohort study.

Bin Zhang, Yanyun Lin, Chao Wang, Zexian Chen, Tianze Huang, Hao Chen, Guannan Wang, Ping Lan, Xiaowen He, Xiaosheng He.

   BACKGROUND: Current guidelines only propose the importance of perineural invasion(PNI) on prognosis in stage II colon cancer. However, the prognostic value of PNI in other stages of colorectal cancer (CRC) is ambiguous.
METHODS: This single-center retrospective cohort study included 3485 CRC patients who underwent primary colorectal resection between January 2013 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University. Associations of PNI with overall survival (OS) and disease-free survival (DFS) were evaluated using multivariable Cox proportional hazards regression models. In addition, interaction analyses were performed to explore the prognostic effects of PNI in different clinical subgroups.
RESULTS: After median follow-up of 61.9 months, we found PNI was associated with poorer OS (adjusted hazard ratio [aHR], 1.290; 95% CI, 1.087-1.531) and DFS (aHR, 1.397; 95% CI, 1.207-1.617), irrespective of tumor stage. Interestingly, the weight of PNI was found second only to incomplete resection in the nomogram for risk factors of OS and DFS in stage II CRC patients. Moreover, OS and DFS were insignificantly different between stage II patients with PNI and stage III patients (both P > 0.05). PNI was found to be an independent prognostic factor of DFS in stage III CRC (aHR: 1.514; 95% CI, 1.211-1.892) as well. Finally, the adverse effect of PNI on OS was more significant in female, early-onset, and diabetes-negative patients than in their counterparts (interaction P = 0.0213, 0.0280, and 0.0186, respectively).
CONCLUSION: PNI was an important prognostic factor in CRC, more than in stage II. The survival of patients with stage II combined with perineural invasion is similar with those with stage III. PNI in stage III CRC also suggests a worse survival.

Keywords:  Colorectal cancer; Perineural invasion; Survival; Tumor stage

DOI:  https://doi.org/10.1186/s12885-023-11114-8
Signal Transduct Target Ther. 2023 Jul 19. 8(1): 275

Cancer cell employs a microenvironmental neural signal trans-activating nucleus-mitochondria coordination to acquire stemness.

Bin He, Rui Gao, Shasha Lv, Ailin Chen, Junxiu Huang, Luoxuan Wang, Yunxiu Feng, Jiesi Feng, Bing Liu, Jie Lei, Bing Deng, Bin He, Bai Cui, Fei Peng, Min Yan, Zifeng Wang, Eric W-F Lam, Bilian Jin, Zhiming Shao, Yulong Li, Jianwei Jiao, Xi Wang, Quentin Liu.

Cancer cell receives extracellular signal inputs to obtain a stem-like status, yet how tumor microenvironmental (TME) neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive. Here, a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element (CRE) transcription factors are convergent activators for cancer stemness. Deconvolution of transcriptomic profiles, specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity. Specifically, neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis, where ATF1 serves as a conserved hub. Upon activation by norepinephrine, ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM, thereby orchestrating nuclear reprograming and mitochondrial rejuvenating. Accordingly, single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells. These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program, suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.

DOI: https://doi.org/10.1038/s41392-023-01487-4
BMJ Case Rep. 2023 Jul 20. pii: e255118. [Epub ahead of print]16(7):

Rare giant schwannoma of superficial peroneal nerve on the dorsum of foot.

Yashavanth Kumar, Aanchal Bhatia, Shiv Manik Ajoy, Dev Anand Galagali.

  Schwannoma is a benign tumour of Schwann cells originating from myelin sheath of axons of the nerves. It is usually seen in the vestibular region, very rarely found in extremity regions. Schwannomas are termed 'Giant' when they measure more than five centimetres in a minimum of one dimension. Giant schwannomas in the foot and ankle region are extremely uncommon. Only eight cases of such a condition are reported. This is a case report of a giant schwannoma found arising from the superficial peroneal nerve in the dorsolateral aspect of the foot. This swelling was excised completely and the diagnosis was confirmed by histopathology.

Keywords:  Neurooncology; Pathology; Surgical oncology

DOI:  https://doi.org/10.1136/bcr-2023-255118
Acta Neurochir (Wien). 2023 Jul 19.

7T for clinical imaging of benign peripheral nerve tumors: preliminary results.

Kimberly K Amrami, Venkata V Chebrolu, Joel P Felmlee, Matthew A Frick, Garret M Powell, Tomas Marek, Benjamin M Howe, Andrew J Fagan, Peter D Kollasch, Robert J Spinner.

   PURPOSE: MRI has become an essential diagnostic imaging modality for peripheral nerve pathology. Early MR imaging for peripheral nerve depended on inferred nerve involvement by visualizing downstream effects such as denervation muscular atrophy; improvements in MRI technology have made possible direct visualization of the nerves. In this paper, we share our early clinical experience with 7T for benign neurogenic tumors.
MATERIALS: Patients with benign neurogenic tumors and 7T MRI examinations available were reviewed. Cases of individual benign peripheral nerve tumors were included to demonstrate 7T MRI imaging characteristics. All exams were performed on a 7T MRI MAGNETOM Terra using a 28-channel receive, single-channel transmit knee coil.
RESULTS: Five cases of four pathologies were selected from 38 patients to depict characteristic imaging features in different benign nerve tumors and lesions using 7T MRI.
CONCLUSION: The primary advantage of 7T over 3T is an increase in signal-to-noise ratio which allows higher in plane resolution so that the smallest neural structures can be seen and characterized. This improvement in MR imaging provides the opportunity for more accurate diagnosis and surgical planning in selected cases. As this technology continues to evolve for clinical purposes, we anticipate increasing applications and improved patient care using 7T MRI for the diagnosis of peripheral nerve masses.

Keywords:  7T; Benign; Nerve imaging; Nerve tumor

DOI:  https://doi.org/10.1007/s00701-023-05724-1
Technol Cancer Res Treat. 2023 Jan-Dec;22:22 15330338231186739

Prognostic Predicting Model of Pancreatic Body Tail Carcinoma Using Clinical and CT Radiomic Data.

Peng An, Yong Lin, Junyan Zhang, Yan Hu, Ping Qin, Yingjian Ye, Xiumei Li, Guoyan Feng, Jinsong Wang.

  Objective: To collect the clinical, pathological, and computed tomography (CT) data of 143 accepted surgical cases of pancreatic body tail cancer (PBTC) and to model and predict its prognosis. Methods: The clinical, pathological, and CT data of 143 PBTC patients who underwent surgical resection or endoscopic ultrasound biopsy and were pathologically diagnosed in Xiangyang No.1 People's Hospital Hospital from December 2012 to December 2022 were retrospectively analyzed. The Kaplan-Meier method was adopted to make survival curves based on the 1 to 5 years' follow-up data, and then the log-rank was employed to analyze the survival. According to the median survival of 6 months, the PBTC patients were divided into a group with a good prognosis (survival time ≥ 6 months) and a group with a poor prognosis (survival time < 6 months), and further the training set and test set were set at a ratio of 7/3. Then logistic regression was conducted to find independent risk factors, establish predictive models, and further the models were validated. Results: The Kaplan-Meier analysis showed that age, diabetes, tumor, node, and metastasis stage, CT enhancement mode, peripancreatic lymph node swelling, nerve invasion, surgery in a top hospital, tumor size, carbohydrate antigen 19-9, carcinoembryonic antigen, Radscore 1/2/3 were the influencing factors of PBTC recurrence. The overall average survival was 7.4 months in this study. The multivariate logistic analysis confirmed that nerve invasion, surgery in top hospital, dilation of the main pancreatic duct, and Radscore 2 were independent factors affecting the mortality of PBTC (P < .05). In the test set, the combined model achieved the best predictive performance [AUC 0.944, 95% CI (0.826-0.991)], significantly superior to the clinicopathological model [AUC 0.770, 95% CI (0.615-0.886), P = .0145], and the CT radiomics model [AUC 0.883, 95% CI (0.746-0.961), P = .1311], with a good clinical net benefit confirmed by decision curve. The same results were subsequently validated on the test set. Conclusion: The diagnosis and treatment of PBTC are challenging, and survival is poor. Nevertheless, the combined model benefits the clinical management and prognosis of PBTC.

Keywords:  and metastasis stage; combined model; computed tomography; endoscopic ultrasound biopsy; nerve invasion; node; pancreatic body tail cancer; predictive performance; prognosis; radiomics; tumor; vascular invasion

DOI:  https://doi.org/10.1177/15330338231186739
Ther Deliv. 2023 Jul 18.

Advancements in therapeutic approaches for malignant peripheral nerve sheath tumor.

Elena Millesi, Julian S Rechberger, Huan Wang, Samir Mardini, Robert J Spinner, David J Daniels.

  Tweetable abstract Emerging targeted therapies offer hope for malignant peripheral nerve sheath tumor. Innovative drug delivery enhances potential treatments. #MPNST #TargetedTherapies #TherapeuticDelivery.

Keywords:  MPNST; drug delivery; intratumoral administration; malignant peripheral nerve sheath tumor; targeted therapy

DOI:  https://doi.org/10.4155/tde-2023-0014
Br J Anaesth. 2023 Aug;pii: S0007-0912(23)00032-6. [Epub ahead of print]131(2): 266-275

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

First Study of Perioperative Organ Protection (SPOP1) investigators

   BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery.
METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival.
RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298.
CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival.
CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Keywords:  aged; cancer surgery; inhalation anaesthesia; intravenous anaesthesia; morbidity; propofol; sevoflurane; survival

DOI:  https://doi.org/10.1016/j.bja.2023.01.023