bims-netuvo 2023-10-22 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023–10–22
ten papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

A brain-tumor neural circuit controls breast cancer progression in mice.
Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis.
T1 mapping in evaluation of clinicopathologic factors for rectal adenocarcinoma.
MRI features of benign peripheral nerve sheath tumors: how do sporadic and syndromic tumors differ?
Vaginal malignant peripheral nerve sheath tumor treated with complete surgical resection and postoperative radiation therapy.
A Retrospective Analysis of Incidental Gallbladder Cancer on Post-cholecystectomy Pathological Review.
Surgical management of sporadic and schwannomatosis-associated pelvic schwannomas.
Surgical management of malignant melanotic nerve sheath tumors: an institutional experience and systematic review of the literature.
Machine learning-based predictive model for the differential diagnosis of ≤ 5 cm gastric stromal tumor and gastric schwannoma based on CT images.
Gastric schwannoma: Two case reports and review of the literature.

J Clin Invest. 2023 Oct 17. pii: e167725. [Epub ahead of print]

A brain-tumor neural circuit controls breast cancer progression in mice.

Si-Yi Xiong, Hui-Zhong Wen, Li-Meng Dai, Yun-Xiao Lou, Zhao-Qun Wang, Yi-Lun Yi, Xiao-Jing Yan, Ya-Ran Wu, Wei Sun, Peng-Hui Chen, Si-Zhe Yang, Xiao-Wei Qi, Yi Zhang, Guang-Yan Wu.

  Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in mice model of breast cancer. We showed that the tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, newly formed sympathetic nerves were detected in tumors, which established a polysynaptically connected with the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and CeMCRH→LPGi circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, alprazolam, an anti-anxiety drug, was found to be a promising intervention for slowing tumor progression. Furthermore, we showed that manipulation of CeMCRH→LPGi circuit directly regulates the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, then affecting tumor progression by modulating the antitumor immunity. Together, these findings reveal a brain-tumor neural circuit contributing to breast cancer progression and provide new therapeutic insights for breast cancer.

Keywords:  Breast cancer; Neuroscience; Oncology

DOI:  https://doi.org/10.1172/JCI167725
JAMA Dermatol. 2023 Oct 18.

Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis.

Paul R Massey, David M Wang, Fadi Murad, Patrick Mulvaney, Kevin Moore, Jean-Phillip Okhovat, Eleanor Russell-Goldman, William M Lin, Adriano Piris, Shyamala C Huilgol, Emily S Ruiz, Chrysalyne D Schmults.

Importance: Perineural invasion (PNI) is an adverse risk feature in cutaneous squamous cell carcinoma (CSCC) that affects patient prognosis and disease management. However, research comparing different PNI patterns on patient outcomes is limited.
Objective: To compare 4 assessments of PNI in CSCC, their associations with poor outcomes, and implications for their inclusion in the Brigham and Women's Hospital (BWH) staging system.
Design, Setting, and Participants: This retrospective cohort study was performed at a single tertiary care institution and compared 4 PNI assessments: nerve caliber, number of involved nerves per section, PNI maximal depth, and PNI location with respect to tumor. Patients with primary, localized, invasive CSCC with PNI diagnosed between January 1, 2000, and December 31, 2017, were identified via an electronic in-house database. Available pathology slides were secondarily reviewed by study authors. Relevant patient and tumor characteristics and outcomes were abstracted from the medical record. Data analysis was performed between September 6 and October 20, 2022.
Main Outcomes and Measures: Risks of recurrence, disease-specific death, and a composite end point (any poor outcome) were calculated via multivariable stepwise Fine and Gray competing-risks regression. Considered revisions to the BWH staging system were assessed via receiver operating characteristic curves and test characteristics.
Results: This study included 140 patients with CSCC, with a mean (SD) age of 75.1 (11.2) years. More than half of the patients were men (93 [66.4%]), and most identified as White (132 [94.3%]). Of the 4 PNI assessments studied, only involvement of multiple nerves was associated with poor outcomes. Perineural invasion of 5 or more distinct nerves (extensive PNI [ePNI]) was independently associated with local recurrence (subhazard ratio [SHR], 13.83 [95% CI, 3.50-54.62]; P < .001), disease-specific death (SHR, 6.20 [95% CI, 1.59-24.21]; P = .009), and any poor outcome (SHR, 10.21 [95% CI, 2.88-36.15]; P < .001). A revised BWH staging system with substitution of ePNI for large-caliber PNI resulted in improved area under the curve and test characteristics compared with current BWH staging criteria that use nerve caliber as the measure of PNI.
Conclusions and Relevance: The findings of this cohort study suggest that ePNI is the best prognostic measure of PNI. Because ePNI obviated the need for a micrometer and had superior prognostic capacity to nerve caliber in this cohort, ePNI should be considered for inclusion in CSCC tumor staging. Inclusion of ePNI as a high-risk factor in CSCC staging systems may optimize patient selection for primary treatment and adjuvant interventions.

DOI: https://doi.org/10.1001/jamadermatol.2023.3703
Abdom Radiol (NY). 2023 Oct 15.

T1 mapping in evaluation of clinicopathologic factors for rectal adenocarcinoma.

Juan Li, Peisi Kou, Liangjie Lin, Yunfei Xiao, Hongrui Jin, Yong Zhang, Jingliang Cheng.

   OBJECTIVE: T1 mapping has been increasingly applied in the study of tumor. The purpose of this study was to evaluate the value of T1 mapping in evaluating clinicopathologic factors for rectal adenocarcinoma.
MATERIALS AND METHODS: Eighty-six patients with rectal adenocarcinoma confirmed by surgical pathology who underwent preoperative pelvic MRI were retrospectively analyzed. High-resolution T2-weighted imaging (T2WI), T1 mapping, and diffusion-weighted imaging (DWI) were performed. T1 and apparent diffusion coefficient (ADC) parameters were compared among different associated tumor markers, tumor grades, stages, and structure invasion statuses. A receiver operating characteristic (ROC) analysis was estimated.
RESULTS: T1 value showed significant difference between high- and low-grade tumors ([1531.5 ± 84.7 ms] vs. [1437.1 ± 80.3 ms], P < 0.001). T1 value was significant higher in positive than in negative perineural invasion ([1495.7 ± 89.2 ms] vs. [1449.4 ± 88.8 ms], P < 0.05). No significant difference of T1 or ADC was observed in different CEA, CA199, T stage, N stage, lymphovascular invasions, extramural vascular invasion (EMVI), and circumferential resection margin (CRM) (P > 0.05). The AUC under ROC curve of T1 value were 0.796 in distinguishing high- from low-grade rectal adenocarcinoma. The AUC of T1 value in distinguishing perineural invasion was 0.637.
CONCLUSION: T1 value was helpful in assessing pathologic grade and perineural invasion correlated with rectal cancer.

Keywords:  Clinicopathologic factors; Magnetic resonance imaging; Rectal cancer; T1 mapping

DOI:  https://doi.org/10.1007/s00261-023-04045-2
Skeletal Radiol. 2023 Oct 16.

MRI features of benign peripheral nerve sheath tumors: how do sporadic and syndromic tumors differ?

Patrick Debs, Rodrigo Luna, Laura M Fayad, Shivani Ahlawat.

   OBJECTIVES: To compare MRI features of sporadic and neurofibromatosis syndrome-related localized schwannomas and neurofibromas.
METHODS: In this retrospective study, our pathology database was searched for "neurofibroma" or "schwannoma" from 2014 to 2019. Exclusion criteria were lack of available MRI and intradural or plexiform tumors. Qualitative and quantitative anatomic (location, size, relationship to nerve, signal, muscle denervation) and functional (arterial enhancement, apparent diffusion-weighted coefficient) MRI features of sporadic and syndrome-related tumors were compared. Statistical significance was assumed for p < 0.05.
RESULTS: A total of 80 patients with 64 schwannomas (sporadic: 42 (65.6%) v. syndrome-related: 22 (34.4%)) and 19 neurofibromas (sporadic: 7 (36.8%) v. syndrome-related: 12 (41.7%)) were included. Only signal heterogeneity (T2W p=0.001, post-contrast p=0.03) and a diffused-weighted imaging target sign (p=0.04) were more frequent with schwannomas than neurofibromas. Sporadic schwannomas were similar in size to syndrome-related schwannomas (2.9±1.2cm vs. 3.7±3.2 cm, p = 0.6), but with greater heterogeneity (T2W p = 0.02, post-contrast p = 0.01). Sporadic neurofibromas were larger (4.6±1.5cm vs. 3.4±2.4 cm, p = 0.03) than syndrome-related neurofibromas, also with greater heterogeneity (T2W p=0.03, post-contrast p=0.04). Additional tumors along an affected nerve were only observed with syndrome-related tumors). There was no difference in apparent diffusion coefficient values or presence of early perfusion between sporadic and syndrome-related tumors (p > 0.05).
CONCLUSIONS: Although syndrome-related and sporadic schwannomas and neurofibromas overlap in their anatomic, diffusion and perfusion features, signal heterogeneity and presence of multiple lesions along a nerve are differentiating characteristics of syndrome-related tumors.

Keywords:  MR nerve imaging; MRI; Neurofibroma; Neurofibromatosis; Neurogenic tumors; Peripheral nerve sheath tumor; Schwannoma; Schwannomatosis; Soft tissue neoplasms

DOI:  https://doi.org/10.1007/s00256-023-04479-1
J Obstet Gynaecol Res. 2023 Oct 16.

Vaginal malignant peripheral nerve sheath tumor treated with complete surgical resection and postoperative radiation therapy.

Yuka Mizuta, Yuki Kozono, Mayu Asai, Kentaro Sekiyama, Yumiko Yoshioka, Toshihiro Higuchi.

  Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms originating from or differentiating into nerve sheaths of peripheral nerves. Vaginal origin is rare, with only six vaginal primary cases reported to date. A 55-year-old woman presented to our hospital with a 7 cm vulvar mass. Tumor biopsy results were suspicious of sarcoma, and pelvic magnetic resonance imaging and hysterofiberscopy showed that the tumor originated from the lower vagina. The mass was transvaginally excised, and histological examination confirmed the diagnosis of a vaginal MPNST with negative surgical margins. The patient underwent radiotherapy because the risk of recurrence was high, owing to the large tumor size and high mitotic index. The patient remained recurrence-free for 1 year after the primary treatment. This is the first case of a high-risk vaginal MPNST that avoided early disease recurrence with additional radiotherapy after complete tumor resection.

Keywords:  adjuvant radiotherapy; malignant; peripheral nerve sheath tumor; treatment; vagina

DOI:  https://doi.org/10.1111/jog.15817
Cureus. 2023 Oct;15(10): e47249

A Retrospective Analysis of Incidental Gallbladder Cancer on Post-cholecystectomy Pathological Review.

Murat Guner, Tayfun Kaya.

  Background Gallbladder cancer is a rare cancer with a poor prognosis despite all the advances in treatment options and is mostly detected incidentally. In the current literature, re-excision is performed on patients with stage T1b and above, but high mortality rates are still observed. In this study, we aimed to investigate the reasons affecting the prognosis of incidental gallbladder cancer. Methodology Data from 33 patients were retrospectively analyzed. Patient age, sex, preoperative radiologic findings, surgical procedures, margin status, postoperative results with histologic diagnosis, T stage, complications, and mortality were evaluated. Results Of the 33 patients included in the study, 24 (72.7%) were female, nine (27.3%) were male, and the mean age was 66.4 ± 13.4 years. Seventeen (51.5%) patients in our study were aged over 65 years. Age over 65 years was found to have a significant effect on mortality (p = 0.018). In the preoperative ultrasound imaging, 27 (81.8%) patients had gallstones, two (6.1%) patients had gallbladder polyps, 31 (93.9%) had focal or diffuse thickness increases in the gallbladder wall, and nine (27.3%) patients had pericholecystic fluid. The presence of pericholecystic fluid (p = 0.039) and wall thickness (p = 0.006) were found to be associated with mortality. There was perineural invasion and lymphovascular in 17 patients each. Both perineural invasion (p = 0.016) and lymphovascular invasion (p = 0.007) were associated with mortality. Tumor grade was also associated with mortality (p = 0.001). When the prognosis of the patients was evaluated according to the T stage, the increase in the T stage negatively affected the prognosis (p < 0.001). Overall survival was a median of 17 months (95% confidence interval = 10.6-23.3). Conclusions Incidental gallbladder cancer is detected on routine histologic examination of gallbladder specimens after cholecystectomy. Most patients may require re-excision, but the prognosis is still poor in patients who have undergone re-excision. Age >65 years, pericholecystic fluid, T stage, grade, lymphovascular invasion, and perineural invasion had a significant effect on mortality, the presence of which should trigger the option of re-excision to be examined more carefully.

Keywords:  cancer; gallbladder cancer; gallbladder malignancy; incidental cancer; incidental gallbladder cancer; oncologic surgeries

DOI:  https://doi.org/10.7759/cureus.47249
Neurosurg Rev. 2023 Oct 19. 46(1): 275

Surgical management of sporadic and schwannomatosis-associated pelvic schwannomas.

Matthieu Peyre, Julien Gaudric, Isabelle Bernat, Arthur André, Thibault Couture, Michel Kalamarides.

  Pelvic schwannomas are rare tumors that may occur either sporadically or in the context of schwannomatosis. We retrospectively reviewed the charts of patients harboring a pelvic schwannoma under conservative management or operated at our reference center between 2016 and 2023. All patients were operated by a multidisciplinary team, combining a vascular surgeon and a neurosurgeon. Twenty-four patients harboring 33 pelvic tumors were included in the cohort, including 12 patients with sporadic lesions, 2 patients with NF2-related schwannomatosis, and 10 patients with NF2-independent schwannomatosis. Multi-nodular tumors were more frequent in schwannomatosis compared to sporadic cases (p = 0.005). The mean age at diagnosis was 41 years old. Schwannomas were located on branches of the sciatic nerve (23/33, 70%), the femoral nerve (6/33, 18%), and the obturator nerve (4/33, 12%). Over the course of the study, 16 patients were operated, including 11 sporadic cases. The indication for surgery was pain (12/16, 75%) or tumor growth (4/16, 25%). Complete resection was achieved in 14 of 16 patients (87%). The mean post-operative follow-up was 37 months (range: 2-168 months). At last-follow-up, complete pain relief was achieved in all 12 patients with pre-operative pain. Post-operative morbidity included 3 long-term localized numbness and one MRC class 4 motor deficit in a multi-nodular tumor in a schwannomatosis patient. Despite its limited size, our series suggests that nerve-sparing resection of pelvic schwannomas offers satisfying rates of functional outcome both in sporadic and schwannomatosis cases, except for multi-nodular tumors.

Keywords:  Neurofibromatosis type 2; Pelvic; Presacral; Schwannoma; Schwannomatosis; Surgery

DOI:  https://doi.org/10.1007/s10143-023-02186-y
J Neurosurg Spine. 2023 Oct 20. 1-10

Surgical management of malignant melanotic nerve sheath tumors: an institutional experience and systematic review of the literature.

Abdul Karim Ghaith, Sarah E Johnson, Victor Gabriel El-Hajj, Oluwaseun O Akinduro, Marc Ghanem, Gaetano De Biase, Loizos Michaelides, Antonio Bon Nieves, W Richard Marsh, Bradford L Currier, John L Atkinson, Robert J Spinner, Mohamad Bydon.

   OBJECTIVE: Malignant melanotic nerve sheath tumors are rare tumors characterized by neoplastic melanin-producing Schwann cells. In this study, the authors report their institution's experience in treating spinal and peripheral malignant melanotic nerve sheath tumors and compare their results with the literature.
METHODS: Data were collected from 8 patients who underwent surgical treatment for malignant melanotic nerve sheath tumors between 1996 and 2023 at Mayo Clinic and 63 patients from the literature. Time-to-event analyses were performed for the combined group of 71 cases to evaluate the risk of recurrence, metastasis, and death based on tumor location and type of treatment received. Unpaired 2-sample t-tests and Fisher's exact tests were used to determine statistical significance between groups.
RESULTS: Between 1996 and 2023, 8 patients with malignant melanotic nerve sheath tumors underwent surgery at the authors' institution, while 63 patients were identified in the literature. The authors' patients and those in the literature had the same mean age at diagnosis (43 years). At the authors' institution, 5 patients (63%) experienced metastasis, 6 patients (75%) experienced long-term recurrence, and 5 patients (62.5%) died. In the literature, most patients (60.3%) were males, with a peak incidence between the 4th and 5th decades of life. Nineteen patients (31.1%) were diagnosed with Carney complex. Nerve root tumors accounted for most presentations (n = 39, 61.9%). Moreover, 24 patients (38.1%) had intradural lesions, with 54.2% (n = 13) being intramedullary and 45.8% (n = 11) extramedullary. Most patients underwent gross-total resection (GTR) (n = 41, 66.1%), followed by subtotal resection (STR) (n = 12, 19.4%), STR with radiation therapy (9.7%), and GTR with radiation therapy (4.8%). Sixteen patients (27.6%) experienced metastasis, 23 (39.7%) experienced recurrence, and 13 (22%) died. Kaplan-Meier analyses showed no significant differences among treatment approaches in terms of recurrence-free, metastasis-free, and overall survival (p > 0.05). Similar results were obtained when looking at the differences with respect to intradural versus nerve root location of the tumor (p > 0.05).
CONCLUSIONS: Malignant melanotic nerve sheath tumors are rare tumors with a high potential for malignancy. They carry a dismal prognosis, with a pooled local recurrence rate of 42%, distant metastasis rate of 27%, and mortality rate of 26%. The findings from this study suggest a trend favoring the use of GTR alone or STR with radiation therapy over STR alone. Mortality was similar regardless, which highlights the need for the development of effective treatment options to improve survival in patients with melanotic schwannomas.

Keywords:  melanocytic; metastasis; oncology; recurrence; schwannoma; spinal; surgical management; survival

DOI:  https://doi.org/10.3171/2023.8.SPINE23427
Discov Oncol. 2023 Oct 19. 14(1): 186

Machine learning-based predictive model for the differential diagnosis of ≤ 5 cm gastric stromal tumor and gastric schwannoma based on CT images.

Guoxian Chen, Lifang Fan, Jie Liu, Shujian Wu.

  The clinical symptoms of ≤ 5 cm gastric stromal tumor (GST) and gastric schwannoma (GS) are similar, but the treatment regimens are different. This study explored the value of computed tomography (CT) combined with machine learning (ML) algorithms to find the best model to discriminate them. A total of 126 patients with GST ≤ 5 cm and 35 patients with GS ≤ 5 during 2013-2022 were included. CT imaging features included qualitative data (tumor location, growth pattern, lobulation, surface ulcer status, necrosis, calcification, and surrounding lymph nodes) and quantitative data [long diameter (LD); short diameter (SD); LD/SD ratio; degree of enhancement (DE); heterogeneous degree (HD)]. Patients were randomly divided into a training set (n = 112) and test set (n = 49) using 7:3 stratified sampling. The univariate and multivariate logistic regression analysis were used to identify independent risk factors. Five ML algorithms were used to build prediction models: Support Vector Machine, k-Nearest Neighbor, Random Forest, Extra Trees, and Extreme Gradient Boosting Machine. The analysis identified that HDv, lobulation, and tumor growth site were independent risk factors (P < 0.05). We should focus on these three imaging features of tumors, which are relatively easy to obtain. The area under the curve for the SVM, KNN, RF, ET, and XGBoost prediction models were, respectively, 0.790, 0.895, 0.978, 0.988, and 0.946 for the training set, and were, respectively, 0.848, 0.892, 0.887, 0.912, and 0.867 for the test set. The CT combined with ML algorithms generated predictive models to improve the differential diagnosis of ≤ 5 cm GST and GS which has important clinical practical value. The Extra Trees algorithm resulted in the optimal model.

Keywords:  Computed tomography; Gastric schwannoma; Gastric stromal tumor; Gastric tumors; Machine learning

DOI:  https://doi.org/10.1007/s12672-023-00801-4
Radiol Case Rep. 2023 Dec;18(12): 4465-4473

Gastric schwannoma: Two case reports and review of the literature.

Rodrigo Cordeiro, Margarida Morgado, Vera Oliveira, Miguel Bispo, Mireia Castillo-Martin, Celso Matos.

  Gastric schwannomas are rare, slow-growing tumors whose clinical presentation is nonspecific. These are mostly benign, with a low probability of malignant transformation and an excellent prognosis. We present 2 cases of gastric schwannomas with distinct clinical features and imaging patterns, whose therapeutic approach differed. Case 1 is a 73-year-old woman with a voluminous subepithelial lesion in the greater gastric curvature, with predominantly endoluminal growth. Clinically the patient presented with nonspecific abdominal complaints and underwent complete surgical excision. Case 2 is a 69-year-old woman with an exophytic lesion adjacent to the gastric antrum, diagnosed incidentally and managed conservatively, with imaging follow-up, for the last 5 years and stable ever since. This article aims to focus on this rare disease, illustrating its main imaging findings, particularly in magnetic resonance imaging, along with pathological correlation, as well as reviewing the literature, discussing the differential diagnosis, and exploring clinical management and prognosis.

Keywords:  Gastrointestinal stromal tumors; Magnetic resonance imaging; Neurilemmoma; Stomach neoplasms

DOI:  https://doi.org/10.1016/j.radcr.2023.09.048