Apparent Diffusion Coefficient-Based Convolutional Neural Network Model Can Be Better Than Sole Diffusion-Weighted Magnetic Resonance Imaging to Improve the Differentiation of Invasive Breast Cancer From Breast Ductal Carcinoma In Situ

Background and PurposeBreast ductal carcinoma in situ (DCIS) has no metastatic potential, and has better clinical outcomes compared with invasive breast cancer (IBC). Convolutional neural networks (CNNs) can adaptively extract features and may achieve higher efficiency in apparent diffusion coefficient (ADC)-based tumor invasion assessment. This study aimed to determine the feasibility of constructing an ADC-based CNN model to discriminate DCIS from IBC.MethodsThe study retrospectively enrolled 700 patients with primary breast cancer between March 2006 and June 2019 from our hospital, and randomly selected 560 patients as the training and validation sets (ratio of 3 to 1), and 140 patients as the internal test set. An independent external test set of 102 patients during July 2019 and May 2021 from a different scanner of our hospital was selected as the primary cohort using the same criteria. In each set, the status of tumor invasion was confirmed by pathologic examination. The CNN model was constructed to discriminate DCIS from IBC using the training and validation sets. The CNN model was evaluated using the internal and external tests, and compared with the discriminating performance using the mean ADC. The area under the curve (AUC), sensitivity, specificity, and accuracy were calculated to evaluate the performance of the previous model.ResultsThe AUCs of the ADC-based CNN model using the internal and external test sets were larger than those of the mean ADC (AUC: 0.977 vs. 0.866, P = 0.001; and 0.926 vs. 0.845, P = 0.096, respectively). Regarding the internal test set and external test set, the ADC-based CNN model yielded sensitivities of 0.893 and 0.873, specificities of 0.929 and 0.894, and accuracies of 0.907 and 0.902, respectively. Regarding the two test sets, the mean ADC showed sensitivities of 0.845 and 0.818, specificities of 0.821 and 0.829, and accuracies of 0.836 and 0.824, respectively. Using the ADC-based CNN model, the prediction only takes approximately one second for a single lesion.ConclusionThe ADC-based CNN model can improve the differentiation of IBC from DCIS with higher accuracy and less time.

Transanal endoscopic microsurgery in the treatment of patients with benign neoplasms and early rectal cancer

Introduction. Transanal endoscopic microsurgery (tem) is a method that allows the specialists to clearly visualize a tumor and bimanually remove the tumor using a set of special instruments. For a number of patients with a good tumor response to chemoradiation therapy (crt), tem is used as an advanced biopsy technique for tumor verification. The purpose of the study was to analyze the results of tem performed at a. Tsyb mrrc. Material and methods. Between 2015 and 2020, 64 patients (men – 42.2 % and women – 57.8 %) underwent tem. Forty patients had rectal cancer and 25 patients had benign rectal tumors. The indication for tem in patients with rectal cancer was the evidence of tis-t1 tumor by postoperative examination findings (mri and endosonography). Eleven patients with stage ii–iii rectal cancer received chemoradiation therapy. The indication for performing tem after rt in patients with rectal cancer was a good tumor response (mri trg1- 2). For statistical processing, commercial biomedical packages prism 3.1 and instat (graphpad software, inc., san diego, usa) were used. The significance of the differences between the indicators was assessed using the pearson χ2 test. Differences were considered significant if the p value was less than 0.05. Results. The median duration of surgery was 110 minutes (30–385). The volume of blood loss did not exceed 40 ml. Postoperative complications were observed in 15 cases (23.4 %). Grade 3 complications according to the clavien-dindo classification were observed in 5 (7.8 %) cases. Postoperative complications occurred more frequently in patients after crt (10.7 and 18.2 %; p=0.603), however, the differences were not statistically significant. At a median follow-up of 18 months (7–30), local relapses developed in 6 out of 26 (23 %) patients who underwent surgery alone. There were no signs of local recurrence in patients with adenocarcinomas after neoadjuvant chemotherapy and rectal adenomas. When comparing patients with the depth of tumor invasion tis-t1sm2 and t1sm3-t2, local relapses occurred in 1 of 21 (4.7 %) and 5 of 12 (41.6 %) cases, respectively (p=0.015). Conclusion. The analysis of the results of tem interventions in patients with rectal neoplasms allows us to conclude that this method of treatment is a priority for patients with benign rectal neoplasms and early rectal cancer. The method can also be used after rt or crt in patients with tumor invasion ≥t1sm3, provided a complete or almost complete tumor response to the treatment.

Advances in Drugs Targeting Lymphangiogenesis for Preventing Tumor Progression and Metastasis

Metastasis of cancer cells from the primary tumor to other organs and tissues in the body is the leading cause of death in patients with malignancies. One of the principal ways cancer cells travel is through lymphatic vessels, and tumor invasion into the regional lymph nodes is a hallmark of early metastasis; thus, the formation of especially peritumoral lymphatic vessels is essential for tumor transportation that gives rise to further progression. In the past few decades, tumor-induced lymphangiogenesis has been testified to its tight correlation with lymphatic metastasis and poor clinical outcomes in multiple types of human malignancies, which warrants novel potential therapeutic targets for cancer treatment. As the understanding of underlying molecular mechanisms has grown tremendously over the years, an inexorable march of anti-lymphangiogenic therapy also aroused terrific interest. As a result, a great number of drugs have entered clinical trials, and some of them exhibited predominant contributions in cancer management. Herein, this review provides an updated summary of the current advances in therapies preventing lymphatic metastasis and discusses the validity of different applications.

Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma

Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal cells including astrocytes, microglia, fibroblasts, pericytes and endothelial cells, supporting tumor progression. Further microglia and macrophages associated with GBMs infiltrate the tumor. These innate immune cells are meant to participate in tumor surveillance and eradication, but they become compromised by GBM cells and exploited in the process. In this review we discuss the context of the GBM microenvironment together with the actions of flavonoids, which have attracted scientific attention due to their pharmacological properties as possible anti-tumor agents. Flavonoids act on a variety of signaling pathways, counteracting the invasion process. Luteolin and rutin inhibit NFκB activation, reducing IL-6 production. Fisetin promotes tumor apoptosis, while inhibiting ADAM expression, reducing invasion. Naringenin reduces tumor invasion by down-regulating metalloproteinases expression. Apigenin and rutin induce apoptosis in C6 cells increasing TNFα, while decreasing IL-10 production, denoting a shift from the immunosuppressive Th2 to the Th1 profile. Overall, flavonoids should be further exploited for glioma therapy.

Qualitative and Quantitative Analysis of Tumor Cell Invasion Using Au Clusters

Tumor invasion/metastasis is still the major cause of death in cancer patients. Membrane type-1 matrix metalloproteinase (MT1-MMP) is directly related to tumor invasion/metastasis. To accurately and quickly distinguish the risk of invasion/metastasis of primary tumor cells, it is urgent to develop a simple and precise quantitative method to distinguish the expression level of MT1-MMP. In this work, we have constructed red fluorescent Au clusters with peroxidase-like properties that could specifically bind to MT1-MMP on human cervical cancer cells. After MT1-MMP was labelled with Au clusters, we could visually see red fluorescence of MT1-MMP on cervical cancer cells via fluorescence microscopy and catalytic color imaging using an ordinary optical microscope. The constructed Au clusters contained 26 Au atoms; thus, the amount of MT1-MMP on cervical cancer cells could be accurately quantified using inductively coupled plasma mass spectrometry (ICP-MS). More importantly, the invasion/metastasis capabilities of the cervical cancer Siha, Caski and Hela cells with different MT1-MMP amounts could be accurately distinguished by fluorescence/catalysis qualitative imaging and ICP-MS quantitative analysis. This method of qualitative/quantitative analysis of tumor-associated proteins on cancer cells has great potential for accurately diagnosing aggressive tumor cells and assessment of their invasion/metastasis risk.

Elevated P-Element-Induced Wimpy-Testis-Like Protein 1 Expression Predicts Unfavorable Prognosis for Patients with Various Cancers

Increasing evidence has shown that overexpression of P-element-induced wimpy-testis (PIWI)-like protein 1 (PIWIL1) was associated with unfavorable prognosis of patients with various types of cancers. Herein, we conducted this meta-analysis to identify the clinicopathological and prognostic value of the PIWIL1 expression in cancers. Three electronic databases (PubMed, Web of Science, and Embase) were comprehensively retrieved for relevant studies up to August 4th, 2019. RevMan 5.3 and STATA 12.0 statistical software programs were used to explore the relationships between PIWIL1 expression and the prognosis and clinicopathological features in cancer patients. A total of 13 studies recruiting 2179 patients with 9 types of solid tumors were finally included in the meta-analysis. The results indicated that patients with high PIWIL1 expression tended to have a shorter survival, and additionally deeper tumor invasion, higher clinical stage, and more lymph node metastasis. PIWIL1 could serve as a biomarker for prognosis and clinicopathological characteristics in various cancers.

Locoregional Extension Patterns of Nasopharyngeal Carcinoma Detected by FDG PET/MR

PurposeWe sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation.MethodsBetween May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study.ResultsThe high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients.ConclusionsFor NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.