bims-netuvo 2022-10-23 papers

J Theor Biol. 2022 Oct 18. pii: S0022-5193(22)00292-2. [Epub ahead of print] 111301

Tumorigenesis and axons regulation for the pancreatic cancer: A mathematical approach.

Sophie Chauvet, Florence Hubert, Fanny Mann, Mathieu Mezache.

The nervous system is today recognized to play an important role in the development of cancer. Indeed, neurons extend long processes (axons) that grow and infiltrate tumors in order to regulate the progression of the disease in a positive or negative way, depending on the type of neuron considered. Mathematical modelling of this biological process allows to formalize the nerve-tumor interactions and to test hypotheses in silico to better understand this phenomenon. In this work, we introduce a system of differential equations modelling the progression of pancreatic ductal adenocarcinoma (PDAC) coupled with associated changes in axonal innervation. The study of the asymptotic behavior of the model confirms the experimental observations that PDAC development is correlated with the type and densities of axons in the tissue. We study then the identifiability and the sensitivity of the model parameters. The identifiability analysis informs on the adequacy between the parameters of the model and the experimental data and the sensitivity analysis on the most contributing factors on the development of cancer. It leads to significant insights on the main neural checkpoints and mechanisms controlling the progression of pancreatic cancer. Finally, we give an example of a simulation of the effects of partial or complete denervation that sheds lights on complex correlation between the healthy, pre-cancerous and cancerous cell densities and axons with opposite functions.

Keywords: Asymptotic analysis; Cancer; Dynamical system; Parameter calibration; Sensitivity analysis

DOI: https://doi.org/10.1016/j.jtbi.2022.111301

Ann Clin Lab Sci. 2022 Sep;52(5): 838-842

Perineural Invasion by an Intraductal Papillary Mucinous Neoplasm of Pancreas: A Case Report of an Unusual and Unreported High-Risk Feature of Malignant Progression.

Juhi D Mahadik, Maria Luisa Machado Heredia, Brandon G Smaglo, William E Fisher, Sadhna Dhingra.

Perineural invasion is a frequent histological finding in pancreatic adenocarcinoma. However, perineural invasion by intraductal papillary mucinous neoplasm (IPMN), a precursor lesion of pancreatic adenocarcinoma, has not been reported so far. We report a unique case of perineural invasion by IPMN in a 60-year-old female who underwent pancreatoduodenectomy for high-risk features of IPMN. Histological evaluation showed increased nerve density in the connective tissue of IPMN with multiple foci of perineural invasion by IPMN. In addition, there was a discrete 2 mm focus of invasive carcinoma that did not show perineural invasion. Chemotherapy was started and the patient is disease-free at 29 months follow up. The case illustrates previously unreported neuroplastic alterations and neutrotropism in benign neoplastic component of a malignant IPMN.

Keywords: intraductal papillary mucinous neoplasm; pancreas; perineural invasion

J Plast Surg Hand Surg. 2022 Oct 16. 1-7

Experience of a single center in the treatment of rare malignant peripheral nerve sheath tumors during the years 1991-2021.

Anna Ptchelintseva, Henrik Nuutinen, Juho Salo, Erkki Tukiainen.

Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma with a poor prognosis, as the aggressive types of this cancer tend to grow rapidly and metastasize frequently. MPNST is associated with neurofibromatosis type 1 gene mutation. The minority of cases arise secondary to radiation therapy or sporadically. The primary treatment for MPNST is early surgical resection of the tumor. The aim of this study was to retrospectively evaluate the outcome of the treatment of MPNST in Helsinki University Hospital from the years 1991 to 2021. Fourteen MPNST cases were evaluated in this study retrospectively. Descriptive statistical analysis was performed on the collected patient data. Marginal resection was completed in nine cases, wide margins were achieved in three cases, and in two cases the final histological examination of the specimen revealed intralesional removal. During the follow-up time of 36.7 ± 12.1 months, all patients who underwent wide margin resection were alive. One patient died 22 months after intralesional resection and six within 38.3 ± 30.9 months of marginal resection. Seventy-one percent of tumor surgeries resulted in Clavien-Dindo class 3b complications, reflecting the complexity of the surgeries. The aggressive nature of MPNST and the large size of these tumors requires extensive surgery, which can lead to complications. The prognosis of MPNST needs improvement.

Keywords: NF1; Resection margin; adjuvant treatment; reconstructive surgery

DOI: https://doi.org/10.1080/2000656X.2022.2131559

J Gastrointest Cancer. 2022 Oct 17.

Validation of the Neoadjuvant Rectal Cancer (NAR) Score for Prognostication Following Total Neoadjuvant Therapy (TNT) for Locally Advanced Rectal Cancer.

Shivani Shah, Palash Asawa, Stephen Abel, Rodney E Wegner.

PURPOSE: The neoadjuvant rectal cancer (NAR) score is a prognostic tool for locally advanced rectal cancer (LARC) treated with total neoadjuvant therapy (TNT). It has been previously validated as an endpoint that predicts survival more accurately than pathologic complete response (pCR) and is the primary endpoint of the ongoing NRG-GI002 Phase II trial. Using the National Cancer Database (NCDB), we aimed to validate the NAR score's ability to predict survival in a large hospital-based dataset.
METHODS: We queried the NCDB to identify locally advanced rectal cancer patients from 2004 to 2015 that received TNT followed by surgical resection. Overall survival (OS) was calculated using Kaplan-Meier curves evaluating NAR score and pCR separately. A multivariable Cox proportional hazards model was used to identify factors associated with survival. Multivariate regression was used to evaluate characteristics associated with a favorable (< 14.98) NAR score.
RESULTS: From > 264,000 patients diagnosed with rectal adenocarcinoma in the NCDB, our final cohort yielded 209 patients with a median age of 62 years. Factors associated with worse survival included age > 62 years old (p = 0.04), lower income (p = 0.03), and unfavorable (≥ 14.98) NAR score (p = 0.04). On multivariate regression, tumors with perineural invasion and a higher comorbidity score (> 1) were less likely to have a favorable NAR response (p = 0.01 and p = 0.01). pCR was not associated with improved survival (p = 0.09).
CONCLUSIONS: Our study validates the NAR score as a prognostic tool in patients receiving TNT for LARC. Tumors with perineural invasion and patients with a higher comorbidity score had worse NAR scores.

Keywords: Locally advanced rectal cancer (LARC); Neoadjuvant rectal cancer (NAR) score; Prognostic tools; Rectal cancer

DOI: https://doi.org/10.1007/s12029-022-00868-2

BMC Cancer. 2022 Oct 15. 22(1): 1063

A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease.

BACKGROUND: Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão.
METHODS: A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67.
RESULTS: Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank).
CONCLUSIONS: Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.

Keywords: Brazil; HPV; Ki-67; Maranhão; Penile cancer; p16; p53

DOI: https://doi.org/10.1186/s12885-022-10127-z