bims-netuvo 2022-09-11 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2022‒09‒11
fourteen papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance.
Genetic Mouse Models to Study Pancreatic Cancer-Induced Pain and Reduction in Well-Being.
Clinical Significance of Perineural Invasion in Men with Grade Group 1 Prostate Cancer on Active Surveillance.
Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.
The Role of Neural Signaling in the Pancreatic Cancer Microenvironment.
A nomogram for predicting 10-year cancer specific survival in patients with pathological T3N0M0 rectal cancer.
Magnetic resonance imaging features and clinical course of malignant melanotic nerve sheath tumors: single institution experience over two decades.
Investigation of Ultrasound Parameters for the Differential Diagnosis of Malignant and Benign Peripheral Nerve Sheath Tumors.
Neuroendocrine regulations in tissue-specific immunity: From mechanism to applications in tumor.
Immunohistochemical analysis of a panel of cancer stem cell markers and potential therapeutic markers in pancreatic ductal adenocarcinoma.
Natural History of Brachial Plexus, Peripheral Nerve, and Spinal Schwannomas.
Prevalence and Detection of Actionable BRAF V600 and NRAS Q61 Mutations in Malignant Peripheral Nerve Sheath Tumor by Droplet Digital PCR.
Circadian rhythm in prostate cancer: time to take notice of the clock.
Tumor Characteristics Associated with Lymph Node Metastasis and Prognosis in Patients with ERBB2-Positive Gastric Cancer.

Cancers (Basel). 2022 Aug 23. pii: 4065. [Epub ahead of print]14(17):

The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance.

Yuequn Niu, Sarah Förster, Michael Muders.

  Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI, tumor cells closely interact with the nerve components in the tumor microenvironment and create the perineural niche, which provides a supportive surrounding for their survival and invasion and benefits the nerve cells. Various transcription factors, cytokines, chemokines, and their related signaling pathways have been reported to be important in the progress of PNI. Nevertheless, the current understanding of the molecular mechanism of PNI is still very limited. Clinically, PNI is commonly associated with adverse clinicopathological parameters and poor outcomes for prostate cancer patients. However, whether PNI could act as an independent prognostic predictor remains controversial among studies due to inconsistent research aim and endpoint, sample type, statistical methods, and, most importantly, the definition and inclusion criteria. In this review, we provide a summary and comparison of the prognostic significance of PNI in prostate cancer based on existing literature and propose that a more standardized description of PNI would be helpful for a better understanding of its clinical relevance.

Keywords:  pathogenesis; perineural invasion; predictive factor; prognostic significance; prostate cancer

DOI:  https://doi.org/10.3390/cancers14174065
Cells. 2022 Aug 24. pii: 2634. [Epub ahead of print]11(17):

Genetic Mouse Models to Study Pancreatic Cancer-Induced Pain and Reduction in Well-Being.

Michael Hirth, Yong Xie, Christiane Höper, Amandine Prats, Thilo Hackert, Matthias P Ebert, Rohini Kuner.

  In addition to the poor prognosis, excruciating abdominal pain is a major challenge in pancreatic cancer. Neurotropism appears to be the underlying mechanism leading to neuronal invasion. However, there is a lack of animal models suitable for translationally bridging in vitro findings with clinical trials. We characterized KPC (KrasG12D/+; Trp53R172H/+; P48-Cre) and KPPC (KrasG12D/+; Trp53R172H/R172H; P48-Cre) mice with genetically determined pancreatic ductal adenocarcinoma (PDAC) and compared them with an orthotopic pancreatic cancer mouse model, healthy littermates and human tissue. We analyzed behavioral correlates of cancer-associated pain and well-being, and studied neuronal remodeling and cytokine expression. Histologically, we found similarities between KPC and KPPC tissue with human samples. Compared to healthy littermates, we detect nerve fiber hypertrophy, which was not restricted to a certain fiber type. Interestingly, while KPPC mice showed significantly reduced well-being, KPC mice emerged to be better suited for studying long-lasting cancer pain that emerges over a slow course of tumor progression. To address the neuroinflammatory correlate of loss of well-being, we studied cytokine levels in KPPC mice and observed a significant upregulation of CXCL16, TNFRSF5, CCL24, CXCL1, CCL22, CLL20 and CX2CL1. In summary, we demonstrate that the KPC mouse model is best suited to studying cancer pain, whereas the KPPC model can be employed to study cancer-associated reduction in well-being.

Keywords:  KPC; KPPC; cytokines; nerve hypertrophy; pain; pancreatic ductal adenocarcinoma

DOI:  https://doi.org/10.3390/cells11172634
J Urol. 2022 Sep 08. 101097JU0000000000002963

Clinical Significance of Perineural Invasion in Men with Grade Group 1 Prostate Cancer on Active Surveillance.

Claire M de la Calle, Mufaddal M Mamawala, Patricia Landis, Katarzyna J Macura, Bruce J Trock, Jonathan I Epstein, Christian P Pavlovich.

  PURPOSE: We aimed to evaluate the clinical significance of perineural invasion (PNI) in men on active surveillance (AS) for Grade Group (GG) 1 prostate cancer (PCa).MATERIALS AND METHODS: We identified 1969 men with GG1 PCa and at least 1 follow-up biopsy. A time-dependent Cox model and a logistic regression model were used to assess the association between biopsy-detected PNI and grade reclassification (GR) (defined as the detection of GG≥2 PCa on a surveillance biopsy), and adverse pathology (AP) (defined as GG≥3, seminal vesicle invasion, lymph node involvement) at radical prostatectomy (RP), respectively.
RESULTS: The 198 men with PNI detected during AS had lower rates of GR-free survival than those without PNI (p<0.001). On multivariable analysis PNI was significantly associated with GR (HR 3.25, 95% CI 2.54-4.16, p<0.001); an association that persisted in the multiparametric magnetic resonance imaging (mpMRI) subset. At RP, men with biopsy-detected PNI had more extraprostatic extension than men without PNI (Relative Risk 1.71, 95% CI 1.15-2.56). However, on multivariable analysis biopsy-detected PNI was not associated with AP (OR 0.68, 95% CI 0.27-1.68, p=0.40) and these patients did not exhibit more biochemical recurrence at 5 years (p>0.05).
CONCLUSIONS: PNI during AS was associated with GR. At RP biopsy-detected PNI patients exhibited more EPE but biopsy-detected PNI was not independently associated with more AP. In addition, these patients did not have more biochemical recurrence during follow-up. PNI should not preclude GG1 patients from AS but they may warrant more stringent monitoring.

Keywords:  active surveillance; perineural invasion; prostate cancer

DOI:  https://doi.org/10.1097/JU.0000000000002963
Cancers (Basel). 2022 Aug 25. pii: 4112. [Epub ahead of print]14(17):

Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.

Soo-Yoon Sung, Sung Hwan Kim, Hong Seok Jang, Jin Ho Song, Songmi Jeong, Ji-Han Jung, Jong Hoon Lee.

  We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.

Keywords:  adjuvant chemotherapy; perineural invasion; rectal cancer; recurrence; surgical margin

DOI:  https://doi.org/10.3390/cancers14174112
Cancers (Basel). 2022 Aug 31. pii: 4269. [Epub ahead of print]14(17):

The Role of Neural Signaling in the Pancreatic Cancer Microenvironment.

Ryota Takahashi, Hideaki Ijichi, Mitsuhiro Fujishiro.

  Pancreatic cancer is one of the most lethal malignant diseases. Various cells in the tumor microenvironment interact with tumor cells and orchestrate to support tumor progression. Several kinds of nerves are found in the tumor microenvironment, and each plays an essential role in tumor biology. Recent studies have shown that sympathetic, parasympathetic, and sensory neurons are found in the pancreatic cancer microenvironment. Neural signaling not only targets neural cells, but tumor cells and immune cells via neural receptors expressed on these cells, through which tumor growth, inflammation, and anti-tumor immunity are affected. Thus, these broad-range effects of neural signaling in the pancreatic cancer microenvironment may represent novel therapeutic targets. The modulation of neural signaling may be a therapeutic strategy targeting the whole tumor microenvironment. In this review, we describe the current understanding of the role of nerves in the tumor microenvironment of various cancers, with an emphasis on pancreatic cancer. We also discuss the underlying mechanisms and the possibility of therapeutic applications.

Keywords:  nerve; pancreatic ductal adenocarcinoma; stroma; tumor microenvironment

DOI:  https://doi.org/10.3390/cancers14174269
Front Med (Lausanne). 2022 ;9 977652

A nomogram for predicting 10-year cancer specific survival in patients with pathological T3N0M0 rectal cancer.

Shuang Liu, Shanfei Yang, Haina Yu, Huilong Luo, Gong Chen, Yuanhong Gao, Rui Sun, Weiwei Xiao.

  Background: The pathological T3N0M0 (pT3N0M0) rectal cancer is the earliest stage and has the best prognosis in the locally advanced rectal cancer, but the optimal treatment remains controversial. A reliable prognostic model is needed to discriminate the high-risk patients from the low-risk patients, and optimize adjuvant chemotherapy (ACT) treatment decisions by predicting the likelihood of ACT benefit for the target population.Patients and methods: We gathered and analyzed 276 patients in Sun Yat-sen University Cancer Center from March 2005 to December 2011. All patients underwent total mesorectal excision (TME), without preoperative therapy, and were pathologically proven pT3N0M0 rectal cancer with negative circumferential resection margin (CRM). LASSO regression model was used for variable selection and risk factor prediction. Multivariable cox regression was used to develop the predicting model. Optimum cut-off values were determined using X-Tile plot analysis. The 10-fold cross-validation was adopted to validate the model. The performance of the nomogram was evaluated with its calibration, discrimination and clinical usefulness.
Results: A total of 188 patients (68.1%) had ACT and no patients had adjuvant radiotherapy. Age, monocyte percentage, carbohydrate antigen 19-9, lymph node dissection numbers and perineural invasion (PNI) were identified as significantly associated variables that could be combined for an accurate prediction risk of Cancer Specific Survival (CSS) for pT3N0M0 patients. The model adjusted for CSS showed good discrimination with a C-index of 0.723 (95% CI: 0.652-0.794). The calibration curves showed that the nomogram adjusted for CSS was able to predict 3-, 5-, and 10-year CSS accurately. The corresponding predicted probability was used to stratify high and low-risk patients (10-year CSS: 69.1% vs. 90.8%, HR = 3.815, 95%CI: 2.102-6.924, P < 0.0001). ACT improved overall survival (OS) in the low-risk patients (10-year OS: 91.9% vs. 83.3%, HR = 0.338, 95% CI: 0.135-0.848, P < 0.0001), while it did not exhibit a significant benefit in the high-risk patients.
Conclusion: The present study showed that age, monocyte percentage, carbohydrate antigen 19-9, lymph node dissection numbers and PNI were independent prognostic factors for pT3N0M0 rectal cancer patients. A nomogram based on these prognostic factors effectively predicts CSS in patients, which can be conveniently used in clinical practice. ACT may improve overall survival in the low-risk patients. But the benefit of ACT was not seen in the high-risk patients.

Keywords:  CSS; adjuvant chemotherapy; nomogram; pT3N0M0; rectal cancer

DOI:  https://doi.org/10.3389/fmed.2022.977652
Skeletal Radiol. 2022 Sep 07.

Magnetic resonance imaging features and clinical course of malignant melanotic nerve sheath tumors: single institution experience over two decades.

Henry Kwok, Meera Hameed, Sinchun Hwang.

  OBJECTIVE: To evaluate MR features and clinical course of malignant melanotic nerve sheath tumor (MMNST), previously known as melanotic schwannoma and considered indolent and rarely metastasizing.MATERIALS AND METHODS: This IRB-approved retrospective study searched 31 patients (20 male: 11 female, mean age 48; range 15-76) with histologically confirmed MMNST in a single tertiary cancer center over 22 years. Pre-treatment MR was available in 12 patients and evaluated by two radiologists in consensus regarding lesion location, size, morphology, signal characteristics, contrast enhancement, local invasion, and presence of classic signs of peripheral nerve sheath tumors. Clinical outcomes, including local recurrence, metastasis, and survival, were examined in 12 patients for whom follow-up was available.
RESULTS: The spine was the most frequent site (13/31) among all identified cases. In 12 cases with MR, lesions were well-circumscribed in 11/12 cases, with a mean size of 4.5 cm (2.3-13.0 cm). Ten of 12 cases showed T1 hyperintensity. In 5/9 spinal MRI, tumor involved multiple levels. All lesions showed contrast enhancement, and local bone invasion in > 50%. A dumb-bell shape was common to all spinal lesions. Classical signs of nerve sheath tumors were uncommon. Among 12 patients with a mean follow-up of 4.8 years (range 1.3-10.2 years), six were disease-free, while two had recurrence or metastases, and four had died of metastases.
CONCLUSION: MMNST usually presents as a T1 hyperintense enhancing dumb-bell shaped mass in the spine. Multi-level involvement and bone invasion are common. MMNST is clinically aggressive with high rates of metastases and death.

Keywords:  MRI; Malignant melanotic nerve sheath tumor; Melanotic schwannoma

DOI:  https://doi.org/10.1007/s00256-022-04171-w
J Ultrasound Med. 2022 Sep 09.

Investigation of Ultrasound Parameters for the Differential Diagnosis of Malignant and Benign Peripheral Nerve Sheath Tumors.

Zhenzhen Jin, Kaiping Zhao, Wen Guo, Dandan Wang, Yukun Deng, Tao Chen.

  OBJECTIVES: The objectives were to identify the key features of malignant and benign peripheral nerve sheath tumors (PNSTs) and determine a strategy for differentiating them using sonography.METHODS: Forty-six malignant peripheral nerve sheath tumors (MPNSTs) and 83 benign peripheral nerve sheath tumors (BPNSTs) confirmed by pathology from April 2010 to July 2021 were included. The general data and grayscale and color Doppler ultrasonic manifestations were compared between the two groups. We used single factor, multifactor, and area under the receiver operating characteristic (ROC) curve analyses to extract significant malignant risk factors and then established a scoring system with these factors.
RESULTS: The significant variables identified in univariate analysis (P < .05) were maximum diameter, location, shape, boundary, encapsulation, echogenicity, texture pattern, calcification, entering or exiting nerve, and vascularity. Shape, boundary and vascularity were significant risk factors, and a scoring system was established. The area under the ROC curve (0.925) confirmed the usefulness of the scoring system for differentiating MPNSTs and BPNSTs.
CONCLUSIONS: Ultrasonography is an effective method for differentiating MPNSTs from BPNSTs.

Keywords:  benign peripheral nerve sheath tumors; malignant peripheral nerve sheath tumors; ultrasonography

DOI:  https://doi.org/10.1002/jum.16089
Front Cell Dev Biol. 2022 ;10 896147

Neuroendocrine regulations in tissue-specific immunity: From mechanism to applications in tumor.

Si-Qing Liu, Bei Li, Juan-Juan Li, Si Sun, Sheng-Rong Sun, Qi Wu.

  Immune responses in nonlymphoid tissues play a vital role in the maintenance of homeostasis. Lots of evidence supports that tissue-specific immune cells provide defense against tumor through the localization in different tissue throughout the body, and can be regulated by diverse factors. Accordingly, the distribution of nervous tissue is also tissue-specific which is essential in the growth of corresponding organs, and the occurrence and development of tumor. Although there have been many mature perspectives on the neuroendocrine regulation in tumor microenvironment, the neuroendocrine regulation of tissue-specific immune cells has not yet been summarized. In this review, we focus on how tissue immune responses are influenced by autonomic nervous system, sensory nerves, and various neuroendocrine factors and reversely how tissue-specific immune cells communicate with neuroendocrine system through releasing different factors. Furthermore, we pay attention to the potential mechanisms of neuroendocrine-tissue specific immunity axis involved in tumors. This may provide new insights for the immunotherapy of tumors in the future.

Keywords:  cancer; neuroendocrine regulation; neuropeptide; neurotransmitter; tissue-specific immunity

DOI:  https://doi.org/10.3389/fcell.2022.896147
J Cancer Res Clin Oncol. 2022 Sep 06.

Immunohistochemical analysis of a panel of cancer stem cell markers and potential therapeutic markers in pancreatic ductal adenocarcinoma.

S M Adnan Ali, Yumna Adnan, Saleema Mehboob Ali, Zubair Ahmad, Tabish Chawla, Hasnain Ahmed Farooqui.

  PURPOSE: Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. It is known for its aggressive nature and high mortality rate. This calls for an urgent need of new prognostic and therapeutic markers that can be targeted for personalized treatment of the patient.METHODS: Among 142 patients diagnosed with pancreatic cancers at Aga Khan University Hospital, a total of 62 patients were selected based on their confirmed diagnosis of PDAC. Immunohistochemistry was performed on Formalin-Fixed Paraffin-Embedded (FFPE) sections using selected antibodies (CD44, CD133, L1CAM, HER2, PD-L1, EGFR, COX2 and cyclin D1). All the slides were scored independently by two pathologists as per the set criteria.
RESULTS: Expression of all cancer stem cell markers was found to be significantly associated with one or more potential therapeutic markers. CD44 expression was significantly associated with HER2 (p = 0.032), COX2 (p = 0.005) and EGFR expression (p = 0.008). CD133 expression also showed significant association with HER2 (p = 0.036), COX2 (p = 0.004) and EGFR expression (p = 0.018). L1CAM expression was found to be associated with expression of COX2 (p = 0.017). None of the proteins markers showed association with overall survival of the patient. On the other hand, among the clinicopathological characteristics, histological differentiation (p = 0.047), lymphovascular invasion (p = 0.021) and perineural invasion (p = 0.014) were found to be significantly associated with patient's overall survival.
CONCLUSION: Internationally, this is the first report that assesses the selected panel of cancer stem cell markers and potential therapeutic targets in a single study and evaluates its combined expression. The study clearly demonstrates association between expression of cancer stem cell markers and therapeutic targets hence paves a way for precision medicine for pancreatic cancer patients.

Keywords:  Cancer stem cell markers; Immunohistochemistry; Pakistan; Pancreatic ductal adenocarcinoma; Targeted therapies

DOI:  https://doi.org/10.1007/s00432-022-04315-4
Neurosurgery. 2022 Sep 07.

Natural History of Brachial Plexus, Peripheral Nerve, and Spinal Schwannomas.

Daniel Lubelski, Zach Pennington, Arinze Ochuba, Tej D Azad, Alireza Mansouri, Jaishri Blakeley, Allan J Belzberg.

BACKGROUND: Management of sporadic schwannomas is often dictated by a patient's clinical presentation and the tumor's behavior. For patients who are managed nonsurgically, there are little data available about the expected natural history.OBJECTIVE: To evaluate the natural history and growth patterns of extracranial schwannomas including tumors of the distal peripheral nerves, spine, and brachial plexus.
METHODS: A retrospective review was performed to identify patients with nonsyndromic extracranial schwannomas at a single tertiary care institution diagnosed between 2002 and 2019. Patient data and tumor characteristics including volume were recorded.
RESULTS: Two hundred twenty-seven patients were identified (mean age 51 years, 42% male, average of 27.8-month follow-up). Tumor location was distal peripheral nerve in 82, brachial plexus in 36, and paraspinal in 109. At the time of diagnosis, peripheral lesions were significantly larger than spinal (59 m3 vs 13 cm3) and brachial plexus lesions (15 cm3). Distinct growth patterns were seen with both distal peripheral nerve and spinal lesions; 34/82 peripheral nerve lesions had fast growth (β = 0.176%/day), and 48 had slow growth (β = 0.021%/day; P < .01). Spinal schwannomas similarly had 30 fast-growing (β = 0.229%/day), 16 moderate-growing (β = 0.071%/day), and 63 slow-growing (β = 0.022%/day; P = .03) subtypes. The brachial plexus had relatively homogeneous growth patterns (β = 0.065%/day). Females had 2.9 times greater odds of having the fast-growing subtype.
CONCLUSION: Distinct growth patterns were seen in extracranial sporadic schwannomas based on tumor location and patient demographics. Fast (>80% volume change per year) vs slow (5%-10% per year) tumor growth can often be ascertained within 2 follow-up images. Awareness of these patterns might have implications for patient counseling and therapeutic decision-making.

DOI: https://doi.org/10.1227/neu.0000000000002118
Hum Pathol. 2022 Sep 03. pii: S0046-8177(22)00223-4. [Epub ahead of print]

Prevalence and Detection of Actionable BRAF V600 and NRAS Q61 Mutations in Malignant Peripheral Nerve Sheath Tumor by Droplet Digital PCR.

Erica Y Kao, Kristina M Wakeman, Yu Wu, John M Gross, Eleanor Y Chen, Robert W Ricciotti, Yajuan J Liu, Jose G Mantilla.

  Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with poor prognosis that do not typically respond well to standard chemotherapy. Recently, point mutations involving BRAF V600E have been demonstrated in a subset of MPNST, offering the possibility of targeted treatment. However, the reported prevalence of these alterations is variable. Mutations involving NRAS, which is also involved in the MAPK/ERK pathway and amenable to targeted inhibitors, have not been well characterized in MPNST. In this study, we validated droplet digital polymerase chain reaction (ddPCR) for the detection of BRAF V600E and NRAS Q61 mutations and evaluate the prevalence of BRAF V600E and NRAS Q61 mutations in 79 cases of MPNST, including 45 sporadic, 27 NF-1 associated and 7 radiation-associated tumors. We detected actionable BRAF or NRAS mutations in 3 of 44 (6.8%) sporadic MPNSTs, including 2 BRAF V600 and 1 NRAS Q61 mutations, as well as one NRAS Q61 mutation in a tumor that was ultimately considered to represent melanoma. These 3 cases with positive mutations were exclusively in sporadic, high grade MPNST (FNCLCC grade 3 of 3), with a prevalence of 11.5% in this group (3.8% NRAS Q61 mutations and 7.7% BRAF V600 mutations). None of the tumors associated with NF-1 or prior radiation had detectable mutations in the genes tested. Overall, the prevalence of these alterations offers the possibility of targeted therapy in this aggressive type of sarcoma and suggests the potential benefit of routine clinical testing.

Keywords:  BRAF; Malignant peripheral nerve sheath tumor; NRAS; ddPCR; targeted therapy

DOI:  https://doi.org/10.1016/j.humpath.2022.08.005
Asian J Androl. 2022 Sep 06.

Circadian rhythm in prostate cancer: time to take notice of the clock.

Wei-Zhen Zhu, Qi-Ying He, De-Chao Feng, Qiang Wei, Lu Yang.

  The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.

Keywords:  chronotherapy; circadian clock; circadian rhythm; prostate cancer

DOI:  https://doi.org/10.4103/aja202255
J Oncol. 2022 ;2022 7592046

Tumor Characteristics Associated with Lymph Node Metastasis and Prognosis in Patients with ERBB2-Positive Gastric Cancer.

Ran Xu, Yisheng Zhang, Jun Zhao, Ke Chen, Zhengguang Wang.

Gastric cancers (GCs) that express human erb-b2 receptor tyrosine kinase 2 (ERBB2, also known as HER2) account for 7.3%-20.2% of GCs. The pathological and prognostic factors associated with lymph node metastasis of such tumors are still unclear. Therefore, we aimed to identify the risk factors for lymph node metastasis and prognostic factors of patients with ERBB2-positive GC. We conducted a retrospective analysis of pathological specimens after D2 radical surgery for locally advanced GC and D1+ surgery performed for early GC in our hospital from January 2015 to December 2018. Patients with ERBB2-positive GC were selected and the potential risk factors for lymph node metastasis and potential factors affecting prognosis were evaluated. Among 1,124 GC patients, 122 diagnosed with ERBB2-positive GC were included in the study. We found that risk factors for lymph node metastasis included tumor size (hazard ratio (HR)- 6.213, 95% confidence interval (CI)- 2.097-18.407, p = 0.001), neural invasion (HR- 2.876, 95% CI - 1.011-8.184, p = 0.048), and vascular invasion (HR- 16.881, 95% CI - 5.207-54.727, p < 0.001). T stage (HR- 4.615, 95% CI - 2.182-9.759, p < 0.001) and vascular invasion (HR- 3.036, 95% CI - 1.369-6.736, p = 0.006) were significant prognostic variables. These findings shed new light on the pathology and prognosis of patients with ERBB2-positive GC.

DOI: https://doi.org/10.1155/2022/7592046