bims-netuvo 2022-06-26 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2022–06–26
ten papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

The Role of Nerve Fibers in the Tumor Immune Microenvironment of Solid Tumors.
Beta-adrenergic receptor blockers and hepatocellular carcinoma survival: a systemic review and meta-analysis.
Inclusion of Perineural Invasion with AJCC-TNM Staging: Outcomes from a South Asian Cohort of Curatively Treated Gastric Cancer Patients.
Prognostic Significance of Perineural Invasion in Patients with Stage II/III Gastric Cancer Undergoing Radical Surgery.
Preoperative Platelet Count Correlates With Postoperative Perineural Invasion on Specimen in Patients Treated With Radical Prostatectomy.
Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update.
Peking Prognostic Score, Based on Preoperative Sarcopenia Status, Is a Novel Prognostic Factor in Patients With Gastric Cancer.
β2-adrenergic receptor drives the metastasis and invasion of pancreatic ductal adenocarcinoma through activating Cdc42 signaling pathway.
Gastric cancer with concurrent pancreatic schwannoma: A case report.
Gastric Malignant Peripheral Nerve Sheath Tumor in Type 1 Neurofibromatosis.

Adv Biol (Weinh). 2022 Jun 25. e2200046

The Role of Nerve Fibers in the Tumor Immune Microenvironment of Solid Tumors.

Sharia Hernandez, Alejandra G Serrano, Luisa M Solis Soto.

  The importance of neurons and nerve fibers in the tumor microenvironment (TME) of solid tumors is now acknowledged after being unexplored for a long time; this is possible due to the development of new technologies that allow in situ characterization of the TME. Recent studies have shown that the density and types of nerves that innervate tumors can predict a patient's clinical outcome and drive several processes of tumor biology. Nowadays, several efforts in cancer research and neuroscience are taking place to elucidate the mechanisms that drive tumor-associated innervation and nerve-tumor and nerve-immune interaction. Assessment of neurons and nerves within the context of the TME can be performed in situ, in tumor tissue, using several pathology-based strategies that utilize histochemical and immunohistochemistry principles, hi-plex technologies, and computational pathology approaches to identify measurable histopathological characteristics of nerves. These features include the number and type of tumor associated nerves, topographical location and microenvironment of neural invasion of malignant cells, and investigation of neuro-related biomarker expression in nerves, tumor cells, and cells of the TME. A deeper understanding of these complex interactions and the impact of nerves in tumor biology will guide the design of better strategies for targeted therapy in clinical trials.

Keywords:  cancer; nerve density; perineural niche; tumor microenvironment; tumor-associated nerves

DOI:  https://doi.org/10.1002/adbi.202200046
Clin Exp Med. 2022 Jun 23.

Beta-adrenergic receptor blockers and hepatocellular carcinoma survival: a systemic review and meta-analysis.

Hyun Chang, Sung Hyun Lee.

   INTRODUCTION: Preclinical data have revealed that beta-adrenergic stimulation can affect the growth and progression of different types of malignancies. Beta-adrenergic receptor blockers have been associated with improved survival in patients with many types of cancer. We performed a meta-analysis to investigate the association between beta-blocker use and hepatocellular carcinoma (HCC) prognosis.
METHODS: In this meta-analysis, a full search was conducted using PubMed, the Cochrane library and Embase to identify all relevant studies published up to May 2021. Available hazard ratios (HRs) were extracted for overall survival (OS), cancer-specific survival (CSS) and pooled using a random-effects meta-analysis.
RESULTS: Four studies involving 7252 patients with HCC met the inclusion criteria and were included in the systemic review. Three studies that reported OS data of 5148 patients were included in the meta-analysis. The random-effects model showed that beta-blocker use was associated with significantly improved OS in HCC (HR = 0.69, 95% CI = 0.54-0.88, P = 0.0031), without significant heterogeneity (I2 = 41%; Q = 6.42, P = 0.18).
CONCLUSION: This meta-analysis suggested that beta-blocker use can be associated with prolonged OS of patients with HCC.

Keywords:  Beta-blocker; Hepatocellular carcinoma; Meta-analysis; Survival

DOI:  https://doi.org/10.1007/s10238-022-00842-z
J Gastrointest Cancer. 2022 Jun 24.

Inclusion of Perineural Invasion with AJCC-TNM Staging: Outcomes from a South Asian Cohort of Curatively Treated Gastric Cancer Patients.

Dillip Kumar Muduly, Madhabananda Kar, Mahesh Sultania, Mohammed Shahin, Susama Patra, Vishwajeet Singh, Mohammed Imaduddin, Sudipta Mohakud, Hemant Kumar Nayak, Manas Kumar Panigraphi, Saroj Kumar Das Majumdar, Dilip Kumar Parida.

   BACKGROUND: The incidence of perineural invasion (PNI) in patients with gastric cancer (GC) is high, and patients with PNI positive disease have a poor prognosis compared to PNI-negative disease. The present study aims to study the incidence and evaluate the impact of PNI on the survival outcome of a cohort of South Asian GC patients.
MATERIAL AND METHODS: All consecutive patients undergoing curative gastrectomy were included in the study. The incidence of PNI and correlation with different clinico-pathological features and overall survival was performed.
RESULTS: A total of 59.54% had PNI-positive disease and the median OS of PNI + ve patients was 29.3 months, while it was not reached in PNI-ve patients. The PNI positivity was a significant prognostic factor for overall survival both on univariate and multivariate analysis. On TNM-PNI staging, those with TNM stage I/II patients with PNI + ve disease had similar OS to all stage III patients (p = 0.835) and were worse than that of PNI-ve patients (p < 0.05).
CONCLUSION: The incidence of PNI in gastric cancer is high. The inclusion of PNI with AJCC-TNM staging may better stratify prognostic staging in curatively treated gastric cancer patients.

Keywords:  Neoplasm staging; Perineural invasion; Prognosis; Stomach neoplasms; Survival

DOI:  https://doi.org/10.1007/s12029-022-00838-8
J Pers Med. 2022 Jun 12. pii: 962. [Epub ahead of print]12(6):

Prognostic Significance of Perineural Invasion in Patients with Stage II/III Gastric Cancer Undergoing Radical Surgery.

Yi-Fu Chen, Shan-Yu Wang, Puo-Hsien Le, Tsung-Hsing Chen, Chia-Jung Kuo, Chun-Jung Lin, Wen-Chi Chou, Ta-Sen Yeh, Jun-Te Hsu.

  The prognostic significance of perineural invasion in patients with gastric cancer (GC) is controversial. This study aimed to determine the prognostic value of perineural invasion in patients with stage II/III GC undergoing radical surgery. A total of 1913 patients with stage II/III GC who underwent curative resection between 1994 and 2015 were recruited. Clinicopathological factors, tumor recurrence patterns, disease-free survival, and cancer-specific survival were compared in terms of perineural invasion. The prognostic factors of disease-free survival and cancer-specific survival were determined using univariate and multivariate analyses. Perineural invasion was found in 57.1% of the patients. Age of <65 years, female sex, large tumor size, upper tumor location, total gastrectomy, advanced tumor invasion depth and nodal involvement, greater metastatic to examined lymph node ratio, undifferentiated tumor, and presence of lymphatic or vascular invasion were significantly associated with perineural invasion. The patients with perineural invasion had higher locoregional/peritoneal recurrence rates than those without. Perineural invasion was independently associated with disease-free survival and cancer-specific survival. In conclusion, perineural invasion positivity is associated with aggressive tumor behaviors and higher locoregional/peritoneal recurrence rates in patients with stage II/III GC undergoing curative surgery. It is an independent unfavorable prognostic factor of disease recurrence and cancer-specific survival.

Keywords:  gastric cancer; perineural invasion; prognostic factor; survival

DOI:  https://doi.org/10.3390/jpm12060962
Front Oncol. 2022 ;12 906936

Preoperative Platelet Count Correlates With Postoperative Perineural Invasion on Specimen in Patients Treated With Radical Prostatectomy.

Fangming Wang, Fei Liu, Jing Liang, Feiya Yang, Nianzeng Xing.

   Objective: It has been reported that perineural invasion (PNI) after radical prostatectomy (RP) is associated with unfavorable prostate cancer (PCa) prognosis. However, the clinicopathological factors especially hematological parameters that influenced PNI remain unknown. Our aim was to explore the relationship between clinicopathological parameters and PNI in patients who underwent RP.
Methods: A total of 348 patients with PCa who underwent RP at our center between 2018 and 2021 were consecutively collected. We divided them into non-PNI and PNI groups based on PNI status and compared clinicopathological characteristics including hematological parameters between non-PNI and PNI groups. The association of clinicopathological parameters including whole blood parameters, age, body mass index (BMI), hypertension, diabetes mellitus, prostate-specific antigen (PSA), ISUP (International Society of Urological Pathology) grade, pathological stage T (pT), and neoadjuvant hormonal therapy (NHT) with PNI was determined by univariate and multivariate logistic regression analyses.
Results: The pathological results of the RP specimen consisted of 254 (73.0%) patients with PNI and 94 (27.0%) cases without PNI. The level of PSA, percentages of advanced pT and grade, positive surgical margin rate, and vessel carcinoma embolus rate were significantly higher in the PNI group when compared with non-PNI counterpart (p = 0.007, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). Among the whole blood parameters, only platelet count and plateletcrit were significantly different [216 (178.8-252.0) vs. 200.5 (173.5-236.5), p = 0.04; 0.0021 (0.0018-0.0025) vs. 0.0020 (0.0017-0.0023), p = 0.008, respectively]. Univariate logistic regression analysis demonstrated that platelet, ISUP, and pT were all positively correlated with the presence of PNI (T3 vs. T1, odds ratio (OR) = 2.029, p = 0.020; OR = 1.697, p < 0.001; OR = 3.836, p < 0.001). In the stepwise multivariate regression analysis, the association between platelet and PNI remained significant (T2 vs. T1, OR = 2.171, 95% CI: 1.082-4.354, p = 0.029; T3 vs. T1, OR = 2.595, 95% CI: 1.259-5.349, p = 0.010) after adjusting for confounding factors including age, BMI, hypertension, diabetes mellitus, PSA, ISUP, pT, and NHT.
Conclusions: The study first revealed that platelet count rather than other whole blood parameters was independently associated with the presence of PNI in patients with PCa, suggesting that platelets might play an essential role in PCa aggressiveness.

Keywords:  correlation; perineural invasion; platelet; radical prostatectomy; specimen

DOI:  https://doi.org/10.3389/fonc.2022.906936
Diagnostics (Basel). 2022 Jun 14. pii: 1463. [Epub ahead of print]12(6):

Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update.

Gaetano Magro, Giuseppe Broggi, Giuseppe Angelico, Lidia Puzzo, Giada Maria Vecchio, Valentina Virzì, Lucia Salvatorelli, Martino Ruggieri.

  Peripheral nerve sheath tumors encompass a wide spectrum of lesions with different biological behavior, including both benign and malignant neoplasms as well as the recent diagnostic category, i.e., "atypical neurofibromatous neoplasm with uncertain biologic potential" to be used only for NF1 patients. Neurofibromas and schwannomas are benign Schwann-cell-derived peripheral nerve sheath tumors arising as isolated lesions or within the context of classical neurofibromatosis or schwannomatoses. Multiple tumors are a hallmark of neurofibromatosis type 1(NF1) and related forms, NF2-related-schwannomatosis (formerly NF2) or SMARCB1/LZTR1-related schwannomatoses. Perineuriomas are benign, mostly sporadic, peripheral nerve sheath tumors that show morphological, immunohistochemical, and ultrastructural features reminiscent of perineurial differentiation. Hybrid tumors exist, with the most common lesions represented by a variable mixture of neurofibromas, schwannomas, and perineuriomas. Conversely, malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or a pre-existing neurofibroma, and in about 50% of cases, these tumors are associated with NF1. The present review emphasizes the main clinicopathologic features of each pathological entity, focusing on the diagnostic clues and unusual morphological variants.

Keywords:  neurofibroma; neurofibromatosis type 1; neurofibromatosis type 2; perineurioma; peripheral nerve sheath tumors; schwannoma; schwannomatosis

DOI:  https://doi.org/10.3390/diagnostics12061463
Front Nutr. 2022 ;9 910271

Peking Prognostic Score, Based on Preoperative Sarcopenia Status, Is a Novel Prognostic Factor in Patients With Gastric Cancer.

Jianping Xiong, Haitao Hu, Wenzhe Kang, Yang Li, Peng Jin, Xinxin Shao, Weikun Li, Yantao Tian.

   Background: This study focused on assessing the role of the Peking prognostic score (PPS), a novel prognostic index based on muscle atrophy and lymphocyte-to-C-reactive protein ratio, within gastric cancer patient prognosis.
Methods: We analyzed the data collected from 774 gastric cancer cases between April 2011 and February 2016 (discovery cohort). The results were assessed in 575 gastric cancer cases from March 2016 to September 2019 (validation cohort). For evaluating skeletal muscle mass, we obtained computed tomography images at the third lumbar vertebra level (L3). We performed a time-dependent receiver operating characteristic curve (t-ROC) to analyze PPS's prognostic significance with others.
Results: The discovery cohort enrolled altogether 774 patients with non-metastatic gastric cancer, including 639 (82.5%) men along with 135 (17.5%) women. The patients were divided into 3 groups; 166 patients (21.4%) were assigned into group 0, 472 (60.9%) in group 1, and 136 (17.7%) in group 2, respectively. An increased PPS was in direct proportion to an elder age, reduced body mass index, higher Pathological Tumor Lymph Node Metastasis stage, perineural invasion, and vascular invasion. We identified PPS to independently estimate patient overall survival (OS) together with disease-free survival (DFS; both P < 0.001). Additionally, as revealed by t-ROC analysis, PPS exhibited the highest sensitivity compared with other prognostic scoring systems in predicting patient survival. Finally, we evaluated the prognostic value of PPS in the validation cohort and confirmed that preoperative PPS independently estimates patient OS and DFS.
Conclusion: The PPS accounts for an efficient nutrition-inflammation prognostic scoring system in gastric cancer patients.

Keywords:  Peking prognostic score; gastric cancer; lymphocyte-to-C-reactive protein ratio; prognostic factors; sarcopenia

DOI:  https://doi.org/10.3389/fnut.2022.910271
J Mol Histol. 2022 Jun 18.

β2-adrenergic receptor drives the metastasis and invasion of pancreatic ductal adenocarcinoma through activating Cdc42 signaling pathway.

Chen Gong, Baoying Hu, Haifeng Chen, Jianxin Zhu, Jinshan Nie, Lu Hua, Long Chen, Yanfei Fang, Cheng Hang, Ye Lu.

  Recent investigations indicate that β2-adrenergic receptor (β2-AR) signaling may facilitate the progression of various tumors, whose underlying mechanisms remain largely elusive. In the present study, we showed that β2-AR recruited Cdc42 in response to isoproterenol (ISO, a β-AR selective agonist) exposure in pancreatic ductal adenocarcinoma (PDAC) cells. The association of β2-AR and Cdc42 promoted the activation of Cdc42, as revealed by increased levels of Cdc42-GTP, and co-incubation with β2-AR antagonist abrogated ISO-induced activation of Cdc42. β2-AR-mediated Cdc42 activation further led to the phosphorylation of downstream PAK1, LIMK1 and Merlin. Furthermore, we showed that the activation of β2-AR/Cdc42 signaling facilitated the migration and invasion of PDAC cells. In addition, β2-AR and Cdc42 were overexpressed in PDAC specimens, compared with adjacent non-tumor tissues. High expression of β2-AR and Cdc42 were correlated with lymph node metastasis and TNM stage in PDAC patients. Finally, we showed that overexpression of β2-AR and Cdc42 were indicative of unfavorable prognosis in PDAC patients. Taken together, our findings suggested that β2-AR might facilitate Cdc42 signaling to drive the migration and invasion of PDAC cells, consequently resulting in the metastasis and dismal prognosis of PDAC. These studies highlight targeting β2-AR/Cdc42 signaling as a therapeutic strategy against PDAC.

Keywords:  Cdc42; Invasion; Metastasis; pancreatic ductal adenocarcinoma; β2-AR

DOI:  https://doi.org/10.1007/s10735-022-10076-8
World J Gastrointest Pathophysiol. 2022 May 22. 13(3): 107-113

Gastric cancer with concurrent pancreatic schwannoma: A case report.

Mateus Barradas Ribeiro, Emerson Shigueaki Abe, André Kondo, Adriana Vaz Safatle-Ribeiro, Marina Alessandra Pereira, Bruno Zilberstein, Ulysses Ribeiro.

   BACKGROUND: The differential diagnosis of abdominal masses is somewhat troublesome, especially when there is a malignancy to be evaluated. We report herein a unique case of gastric adenocarcinoma concurrent with a pancreatic schwannoma. Correct assessment of intraoperative findings is essential for adequate tumor staging and to decide the proper management of a concurrent pancreatic lesion.
CASE SUMMARY: Computed tomography scan performed for gastric cancer staging revealed a solid and cystic pancreatic mass that had no signs of local invasiveness. Surgical resection of the pancreas was decided preoperatively since a radical approach of the gastric tumor could be performed. There were no signs of distant metastases, and the large pancreatic mass was in contact with the posterior gastric wall. Histopathological study revealed a pancreatic schwannoma, which is an uncommon neoplasm that arises from Schwann cells around peripheral nerves.
CONCLUSION: Therefore, pancreatic masses deserve special attention regarding the differential diagnosis in patients with gastric cancer. The presence of a large pancreatic mass should not preclude the potentially curative intent of the gastric cancer treatment.

Keywords:  Case report; Gastric adenocarcinoma; Pancreas; Schwannoma; Stomach neoplasms

DOI:  https://doi.org/10.4291/wjgp.v13.i3.107
Korean J Gastroenterol. 2022 Jun 25. 79(6): 265-269

Gastric Malignant Peripheral Nerve Sheath Tumor in Type 1 Neurofibromatosis.

Hyun Seung Hwang, Yun Jin Jeong, Kyung Han Nam, Sung Jin Oh, Yong Eun Park.

  Gastric malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare spindle cell sarcomas that arise within the peripheral nerves of the gastrointestinal tract. MPNST can present as a mass that may or may not be accompanied by obstruction or bleeding. Type 1 neurofibromatosis (NF) is an autosomal dominant genetic disorder with an incidence of 1 in 2,500-3,000. Plexiform neurofibromas in Type 1 NF can undergo a malignant transformation to MPNSTs. Approximately half of the incidence of MPNST is associated with the NF-1 gene. MPNST behaves aggressively, and radical excisional surgery is important for treatment. Recurrence and metastasis are significant, even after a radical excision. Despite multidisciplinary treatment, the five-year survival rate is only 30-50%. This paper reports the case of a 47-year-old man with Type 1 NF who presented with hemorrhage of a gastric subepithelial lesion. He underwent surgery under the suspicion of a gastrointestinal stromal tumor, but it was diagnosed as MPNST after confirming the histopathological appearance and immunohistochemical profiles. In addition, the large mass invaded the spleen and diaphragm. Radical surgery was performed, and additional chemotherapy was administered. This paper reports the experience of a patient with NF 1 with advanced MPNST discovered due to a subepithelial lesion.

Keywords:  Gastric subepithelial lesion; Malignant peripheral nerve sheath tumor; Neurofibromatosis 1

DOI:  https://doi.org/10.4166/kjg.2022.022