bims-netuvo 2022-12-25 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2022–12–25
nine papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells.
Prognostic value of tumor deposits in lymph node-negative gastric cancer: A propensity score matching study.
Angiosarcoma arising in a schwannoma of the peripheral nervous system: illustrative case.
Surgery Alone (Without Adjuvant Radiation) Adequately Treats Histologic Perineural Basal Cell Carcinomas: A Systematic Review With Meta-Analysis.
Deep Margins Melanoma: How Deep Is Deep Enough?
Association between the CASC16 rs4784227 polymorphism and breast cancer risk and prognosis in a northeast Chinese Han population.
Primary Malignant Peripheral Nerve Sheath Tumor of the Breast: A Rare Case Report and Review of Literature.
Liver Tumor Markers, HALP Score, and NLR: Simple, Cost-Effective, Easily Accessible Indexes for Predicting Prognosis in ICC Patients after Surgery.
Surgical Technique for Superior Cervical Ganglionectomy in a Murine Model.

Cancers (Basel). 2022 Dec 12. pii: 6132. [Epub ahead of print]14(24):

A Novel Therapeutic Target for Small-Cell Lung Cancer: Tumor-Associated Repair-like Schwann Cells.

Shuhui Cao, Yue Wang, Yan Zhou, Yao Zhang, Xuxinyi Ling, Lincheng Zhang, Jingwen Li, Yu Yang, Weimin Wang, Michael R Shurin, Hua Zhong.

  Small-cell lung cancer (SCLC), representing 15-20% of all lung cancers, is an aggressive malignancy with a distinct natural history, poor prognosis, and limited treatment options. We have previously identified Schwann cells (SCs), the main glial cells of the peripheral nervous system, in tumor tissues and demonstrated that they may support tumor spreading and metastasis formation in the in vitro and in vivo models. However, the role of SCs in the progression of SCLC has not been investigated. To clarify this issue, the cell proliferation assay, the annexin V apoptosis assay, and the transwell migration and invasion assay were conducted to elucidate the roles in SCLC of tumor-associated SCs (TA-SCs) in the proliferation, apoptosis, migration, and invasion of SCLC cells in vitro, compared to control group. In addition, the animal models to assess SC action's effects on SCLC in vivo were also developed. The result confirmed that TA-SCs have a well-established and significant role in facilitating SCLC cell cancer migration and invasion of SCLC in vitro, and we also observed that SC promotes tumor growth of SCLC in vivo and that TA-SCs exhibited an advantage and show a repair-like phenotype, which allowed defining them as tumor-associated repair SCs (TAR-SCs). Potential molecular mechanisms of pro-tumorigenic activity of TAR-SCs were investigated by the screening of differentially expressed genes and constructing networks of messenger-, micro-, and long- non-coding RNA (mRNA-miRNA-lncRNA) using DMS114 cells, a human SCLC, stimulated with media from DMS114-activated SCs, non-stimulated SCs, and appropriate controls. This study improves our understanding of how SCs, especially tumor-activated SCs, may promote SCLC progression. Our results highlight a new functional phenotype of SCs in cancer and bring new insights into the characterization of the nervous system-tumor crosstalk.

Keywords:  Schwann cells; gene expression; miRNA; small-cell lung cancer; tumor progression

DOI:  https://doi.org/10.3390/cancers14246132
Eur J Surg Oncol. 2022 Dec 14. pii: S0748-7983(22)01350-6. [Epub ahead of print]

Prognostic value of tumor deposits in lymph node-negative gastric cancer: A propensity score matching study.

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

   BACKGROUND: The purpose of this study was to assess the prognostic value of TD in lymph node-negative GC.
METHODS: A retrospective study was conducted to collect the clinicopathological data from 1224 patients with lymph node-negative GC. According to their TD status, patients were categorized into TD-positive and TD-negative groups. Patients in both groups underwent a 1:1 propensity score matching analysis. Survival analysis was performed by the Kaplan-Meier method, and the differences between survival curves were measured by log-rank test. The cox proportional hazards model was used for univariate and multivariate analyses.
RESULTS: The TD-negative group had higher 5-year overall survival(OS) rate than TD-positive group(69.4%VS.36.4%,P < 0.05). Further subgroup analysis indicated that patients in the TD-negative group had higher 5-year OS rates than those in the TD-positive group in the T1-2, T3, and T4 subgroups(all with P < 0.05).The OS rates were decreased with the increase of the number of TD.The univariate Cox regression analysis demonstrated that tumor location in antrum, distal gastrectomy, perineural invasion, T4-stage,lymphovascular invasion and the number of TD were all associated with prognosis in patients undergoing curative gastric resection (P < 0.05).The multivariable analysis revealed that the number of TD, perineural invasion, lymphovascular invasion and T4 stage were independently associated with OS.
CONCLUSION: In lymph node-negative GC, TD is an independent risk factor for prognosis, regardless of T-stage, and patients with ≥3 TD have a worse prognosis.

Keywords:  Gastric cancer; Negative lymph node; Prognosis; Propensity score matching; Tumor deposits

DOI:  https://doi.org/10.1016/j.ejso.2022.12.004
J Neurosurg Case Lessons. 2022 Dec 19. pii: CASE22452. [Epub ahead of print]4(25):

Angiosarcoma arising in a schwannoma of the peripheral nervous system: illustrative case.

Nikita Lakomkin, Jorge Torres-Mora, Eric J Dozois, Robert J Spinner.

   BACKGROUND: Schwannomas of the peripheral nerves are benign tumors that can very rarely undergo malignant transformation. These lesions are particularly challenging to diagnose via noninvasive techniques but can have significant implications for treatment.
OBSERVATIONS: This is a case of a 70-year-old female with a prior history of a right sciatic notch tumor that was diagnosed as a conventional schwannoma via histology from an initial biopsy and subsequent surgical debulking. Unfortunately, she experienced significant worsening of her motor deficit, whereby her postoperative foot weakness progressed to complete foot drop in less than 2 years. In addition, she demonstrated significant radiological progression, with more than 1 to 2 cm of growth in each dimension at her subsequent evaluation, along with intractable right leg pain. An additional operation was performed to completely remove the 7 × 8 cm tumor, and histology demonstrated angiosarcoma within a schwannoma. There was no evidence of recurrence at 15 months, and the patient had significant improvement in her pain.
LESSONS: Rapidly worsening function and radiological progression are not typically seen with conventional benign nerve sheath tumors and should prompt consideration of other lesions. Angiosarcoma within schwannoma is a rare pathology and optimal therapies for these tumors in terms of surgical timing and adjuvant therapy are still unknown.

Keywords:  hybrid schwannoma; hybrid tumor; nerve tumor

DOI:  https://doi.org/10.3171/CASE22452
Dermatol Surg. 2023 01 01. 49(1): 1-7

Surgery Alone (Without Adjuvant Radiation) Adequately Treats Histologic Perineural Basal Cell Carcinomas: A Systematic Review With Meta-Analysis.

Mark M Ash, Frank A Lacy, Jigar Patel, Rajat Varma.

BACKGROUND: Histologic perineural invasion (PNI) in basal cell carcinomas (BCC) lacks evidence-based treatment guidelines.
OBJECTIVE: Systematically review and analyze treatment outcomes of BCC with histologic PNI (PNBCC).
MATERIALS AND METHODS: PubMed, Embase, and Cochrane Reviews were searched through June 25, 2021. Thirteen eligible cohort studies were meta-analyzed.
RESULTS: 502 of 713 PNBCC were treated with Mohs Surgery (MMS), wide local excision (WLE), or surgery (MMS or WLE) with adjuvant radiation (Surg + RT). Overall 5-year local control (LC) was 97.2% and cancer-specific survival (CSS) was 99.6%. Surg and Surg + RT did not differ in recurrence (2.1% vs 4.7%; p-value 0.56; RR 1.51 [0.37, 6.20]), LC (97.9% vs 96.2%; p-value 0.19; RR 0.98 [0.96, 1.01]) or CSS (100% vs 99.1%; p-value 0.40; RR 0.99 [0.95, 1.02]).
LIMITATIONS: No randomized controlled trials were found. Outcome data were often lacking.
CONCLUSION: Overall LC and CSS were high at median 5-year follow-up for surgery alone and Surg + RT. Surgery alone and Surg + RT demonstrated statistically equivalent outcomes. We do not recommend adjuvant radiation therapy for solely histologic PNBCC if clear margins are achieved.

DOI: https://doi.org/10.1097/DSS.0000000000003640
Am Surg. 2022 Dec 18. 31348221146933

Deep Margins Melanoma: How Deep Is Deep Enough?

Megan L Burger, James M Haggerty, Shengxuan Wang, Jacqueline C Oxenberg.

   BACKGROUND: Wide excision (WE) to muscular fascia for invasive melanoma is common practice but excision to subcutaneous tissue may be adequate. We evaluated practice patterns regarding depth of biopsy and excision as well as risks for recurrence.
METHODS: Retrospective review of patients with pT1-4 melanoma (cN0) treated with WE at a single institution was performed. Patient factors were evaluated. Biopsy and excision techniques were compared to pathology and reviewed for recurrence.
RESULTS: 385 patients from 2006 to 2020 were included. Lesions were on the extremity (n = 189), head/neck (n = 48), trunk (n = 148). Biopsy techniques included shave (n = 330), excisional (n = 36), punch (n = 10), incisional (n = 9). Deep biopsy margins were positive for IM/melanoma in situ in 139 patients. WE specimens were taken to muscular fascia (n = 218) or mid/deep fat (n = 144). 51 patients had recurrent disease or a new primary lesion: locoregional (n = 31), distant (3), or new lesions (n = 17).
DISCUSSION: Patient characteristics associated with recurrence include older age and female gender. Tumor characteristics associated with recurrence include lesions located on the trunk, superficial spreading melanoma, ulceration, perineural invasion, and clinical T and P stage. Patients that recurred were more likely to have WE taken to or including muscular fascia. Biopsy type, deep margin on biopsy, and depth of dissection was not associated with recurrence.

Keywords:  biopsy; margins; melanoma; recurrence; wide excision

DOI:  https://doi.org/10.1177/00031348221146933
PeerJ. 2022 ;10 e14462

Association between the CASC16 rs4784227 polymorphism and breast cancer risk and prognosis in a northeast Chinese Han population.

Yue Zhang, Changgui Kou, Lin Jia, Yangyang Gao, Xin Li, Hao Wu, Naifei Chen, Zheng Lv.

   Background: Breast cancer (BC) poses a serious threat to women worldwide. This research was designed to explore the association between the rs4784227 polymorphism of cancer susceptibility candidate gene 16 (CASC16) and BC susceptibility and prognosis, aiming to provide further information for the early detection of BC and to accelerate comprehensive cancer management.
Methods: A total of 1,733 subjects were recruited for this case-control study, of which 828 are BC patients and 905 are healthy individuals. The relevance between SNP rs4784227 and BC risk in diverse genetic models was analyzed by using the SNPStats analysis program and was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) using the binary logistic regression model. Pearson's χ 2 test was used to determine the correlation between the polymorphism and clinical characteristics of BC patients. Additionally, univariate survival analysis was performed by the Kaplan-Meier method and log-rank test, and multivariate survival analysis was performed by Cox regression.
Results: SNP rs4784227 was significantly associated with susceptibility to BC in the dominant model (CT/TT versus CC, OR = 1.237, 95% CI = 1.012-1.513, P = 0.038). The minor allele of SNP rs4784227 was significantly linked to an increased risk of BC (OR = 1.197, 95% CI = 1.022-1.401, P = 0.026). In addition, the rs4784227 polymorphism of CASC16 was associated with perineural invasion (P = 0.030), menstrual status (P = 0.016) and histological grade (P = 0.001, P = 0.003, P = 0.025; respectively) of BC patients. There was no significant association between the genotypes of rs4784227 and disease-free survival (DFS) or overall survival (OS) of breast cancer patients (P > 0.05).
Conclusions: The rs4784227 polymorphism of CASC16 may affect susceptibility to breast cancer and is associated with perineural invasion, menstrual status and histological grade in BC patients. Additionally, our results could not confirm that this polymorphism was related to breast cancer prognosis.

Keywords:  Breast cancer; CASC16; Prognosis; Single nucleotide polymorphism; Susceptibility

DOI:  https://doi.org/10.7717/peerj.14462
Cureus. 2022 Nov;14(11): e31586

Primary Malignant Peripheral Nerve Sheath Tumor of the Breast: A Rare Case Report and Review of Literature.

Muhammad Tahir, Mohamed Zedan, Vindhya Bellamkonda, Donna L Dyess, Eric X Wei.

  Primary breast sarcomas are uncommon and primary mammary malignant peripheral nerve sheet tumors (MPNST) are exceptionally rare. MPNSTs are malignant variants of peripheral nerve sheath tumors. These neoplasms are often associated with neurofibromatosis type I (NF-I) but can also occur sporadically. They tend to occur in the deeper soft tissues, trunk, and extremities. A 60-year-old Asian female was referred to our surgical clinic for evaluation of a left breast mass and an abnormal mammogram. The patient noticed the mass in the left breast three months earlier and was referred for mammography by her primary physician. Mammography reported partially defined masses in the superior aspect of the left breast, and ultrasound showed a solid mass measuring 5.2 X 3 cm. The mass was 11 cm on clinical exam. Subsequent core biopsy of the left breast lesion showed high-grade malignant neoplasm. Workup showed no evidence of metastatic disease, and the patient underwent modified radical mastectomy. The neoplastic cells were positive for CD99, S-100, SOX-10, neuron specific enolase, p53, vimentin, focally positive for neurofilament, D2-40, p63, and negative for epithelial, melanoma and other sarcoma markers. The tumor was triple negative estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), with Ki-67 at 61%. A diagnosis of primary high grade malignant peripheral nerve sheath tumor of the breast was rendered. The patient does not have a history of NF-1. An accurate diagnosis of this rare entity is necessary because it plays a crucial role in the therapeutic options and prognosis. In our case the patient underwent modified radical mastectomy. The purpose of presenting this unique case is to provide awareness of the existence of this entity among pathologists and clinicians for better patient care.

Keywords:  metaplastic breast cancer; nerve sheet tumor; primary malignant peripheral nerve sheath tumor; sarcoma of breast; variant of metaplastic breast cancer

DOI:  https://doi.org/10.7759/cureus.31586
J Pers Med. 2022 Dec 09. pii: 2041. [Epub ahead of print]12(12):

Liver Tumor Markers, HALP Score, and NLR: Simple, Cost-Effective, Easily Accessible Indexes for Predicting Prognosis in ICC Patients after Surgery.

Deyao Zhang, Huilan Zeng, Yangxun Pan, Yumo Zhao, Xin Wang, Jinbin Chen, Juncheng Wang, Yaojun Zhang, Zhongguo Zhou, Li Xu, Minshan Chen, Dandan Hu.

   INTRODUCTION: To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC).
METHODS: In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis.
RESULTS: The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619).
CONCLUSIONS: Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.

Keywords:  HALP score; NLR; PLR; carbohydrate antigen 19-9; carcinoembryonic antigen; des-gamma-carboxyprothrombin; prognosis

DOI:  https://doi.org/10.3390/jpm12122041
J Vis Exp. 2022 12 02.

Surgical Technique for Superior Cervical Ganglionectomy in a Murine Model.

Qi Wang, Chun-Hao Chen, Hongbo Xu, Sylvie Deborde, Richard J Wong.

Growing evidence suggests that the sympathetic nervous system plays an important role in cancer progression. Adrenergic innervation regulates salivary gland secretion, circadian rhythm, macular degeneration, immune function, and cardiac physiology. Murine surgical sympathectomy is a method for studying the effects of adrenergic innervation by allowing for complete, unilateral adrenergic ablation while avoiding the need for repeated pharmacologic intervention and the associated side effects. However, surgical sympathectomy in mice is technically challenging because of the small size of the superior cervical ganglion. This study describes a surgical technique for reliably identifying and resecting the superior cervical ganglion to ablate the sympathetic nervous system. The successful identification and removal of the ganglion are validated by imaging the fluorescent sympathetic ganglia using a transgenic mouse, identifying post-resection Horner's syndrome, staining for adrenergic markers in the resected ganglia, and observing diminished adrenergic immunofluorescence in the target organs following sympathectomy. This model enables future studies of cancer progression as well as other physiological processes regulated by the sympathetic nervous system.

DOI: https://doi.org/10.3791/64527