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Rosa, Manuela, Angelo Franzini, Gaia Giannicola, Giuseppe Messina, Alfredo Carlo Altamura, and Alberto Priori. "Hypothalamic Oscillations in Human Pathological Aggressiveness." Biological Psychiatry 72, no. 12 (December 2012): e33-e35. http://dx.doi.org/10.1016/j.biopsych.2012.06.007.
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Mamta and Y. Singh. "Variability in pathological characters in Gloeocercospora sorghi isolates from sorghum." INTERNATIONAL JOURNAL OF PLANT PROTECTION 13, no. 2 (October 15, 2020): 148–55. http://dx.doi.org/10.15740/has/ijpp/13.2/148-155.
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Zonate leaf spot caused by Gloeocercospora sorghi Bain and Edgerton (1943) is one of the most destructive diseases of sorghum in India and Uttarakhand is considered as a hot spot for this disease. The present investigation was carried out to record the pathogenic variability of thirty isolates of Gloeocercospora sorghi on five different lines of sorghum. The G. sorghi isolates differed significantly from each other on the basis of pathological attributes viz., latent period, aggressiveness and virulence index and thus, grouped into three virulence categories. The findings suggest that analysis of variance for latent, aggressiveness, per cent disease intensity (PDI) and virulence index showed that the variations in latent period and virulence disease reaction were attributed more to the isolates and aggressiveness to the host lines than to the isolate × host line interactions.
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Mushref, Malek, Matthew Bridges, Keshav Chandran, Rupak Mukherjee, and Mahsa Javid. "PSAT378 Hashimoto's Thyroiditis and Differentiated Thyroid Cancer Aggressiveness." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A845. http://dx.doi.org/10.1210/jendso/bvac150.1747.
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Abstract Background Hashimoto's thyroiditis (HT) is associated with a 1.5-fold increased risk of differentiated thyroid cancer (DTC). It is postulated that the inflammatory milieu in HT may damage thyrocytes, increasing the risk of cancer. However, it is not precisely known how the presence of thyroiditis affects aggressiveness of DTC and if a causal relationship exists. It has been suggested HT may correlate with a less aggressive phenotype with smaller tumor size, lower rate of aggressive variants, less frequent radioactive-iodine administration, and higher rates of clinical remission. The aim of this study was to investigate the pathological features of DTC in patients with HT and whether length of time with HT affects tumor aggression. Method Charts of 367 consecutive patients with DTC undergoing thyroidectomy were reviewed. Clinical and pathological factors were analyzed. A composite score of tumor aggressiveness was calculated using the presence of multifocality, angioinvasion, lymphatic invasion, extrathyroidal extension, central and lateral lymph node (LLN) involvement. This score and tumor size were compared in patients with clinical (elevated thyroid peroxidase or anti-thyroglobulin antibodies) or pathological (presence of inflammation on pathology) HT. Time to surgery from diagnosis of HT was also evaluated. Results In 367 patients with DTC (343 papillary, 29 follicular, 5 both), mean size of the largest tumor was 1.5±1.7cm, mean composite score was 1.3±1.6cm. Seventy-three (19.9%) and 156 (42.5%) patients had clinical or pathological HT, respectively; 92 (25.1%) had preoperative hypothyroidism. Patients with clinical HT alone, or in addition to pathological HT, had a reduced risk of LLN disease (Odds Ratio: 0.21 p<0.005, and OR: 0.43 p=0.01, respectively); those with pathological HT alone had a trend towards lower risk (p=0.06). Neither the overall score for tumor aggressiveness nor tumor size correlated with clinical or pathological HT. Length of time from diagnosis of clinical HT to surgery was not associated with tumor size, aggressiveness or presence of inflammation on pathology. Conclusion Clinical HT is associated with reduced risk for LLN metastasis, supporting the suggestion that presence of HT confers a better prognosis in DTC. Length of time with HT does not alter the risk for aggressive features of DTC indicating lack of an escalating causal relationship. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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Abdou, Yara, Mariko Asaoka, and Kazuaki Takabe. "Pathological and genetic aggressiveness of left-sided breast cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e12579-e12579. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e12579.
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e12579 Background: Breast Cancer in women consistently occurs more frequently in the left breast, with the ratio of left to right sided breast cancer cases ranging from 1.05 to 1.26. In spite of the difference in frequency, prior studies have failed to show any significant difference in clinical characteristics between left sided and right sided cancer. Methods: Genomic and clinical features were collected from The Cancer Genome Atlas breast cancer project. LVI status, mitotic rate, nuclear score and tubular score were collected from pathology reports in TIES client 5.8. Fisher's exact test was used for group comparison and survival analysis was performed with Cox regression. Cytolytic activity (CYT) indicates anti-cancer immune response and was quantified from gene expression data. Hallmark gene-sets were used for gene set enrichment analysis (GSEA). Results: Among the 1081 women with unilateral invasive breast cancer, 561 had tumor on the left side compared to 520 on the right. Our results didn’t show any significant differences between left and right side with regards to tumor location, histology, race, and tumor characteristics including stage, tumor size, nodal status and receptor status. No statistical significant differences were observed in mitotic rate, LVI status and tubular score, however, the tumor grade was significantly higher in the left side. Moreover, there were no significant differences in mutation count, CYT and overall survival between both sides. GSEA revealed cell-cycle related gene sets like G2M checkpoint, Mitotic spindle, E2F targets and MYC targets which were significantly enriched in left sided tumor. Furthermore, out of the 865 genes which were highly expressed on the left side, we identified specific genes including BRCA1, BRCA2, BRIP1, CHEK2, FANCC, PALB2, TP53 and MSH6 which are associated primarily with breast cancer genesis and mostly have established clinical management guidelines. Conclusions: Our results suggest a more aggressive nature to left sided breast cancer with a higher pathological grade perhaps requiring more aggressive treatment. Such a hypothesis needs further study to confirm or refute its validity. If confirmed, it may have a major impact with regard to biology of breast cancer and its subsequent management.
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Sachdev, Perminder, John Sydney Smith, John Matheson, Peter Last, and Peter Blumbergs. "Amygdalo-Hippocampectomy for Pathological Aggression." Australian & New Zealand Journal of Psychiatry 26, no. 4 (December 1992): 671–76. http://dx.doi.org/10.3109/00048679209072105.
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Two patients are reported, one with severe brain damage and epilepsy, and the other with limbic epilepsy, who were treated with unilateral microsurgical amygdalo-hippocampectomy for the control of rage and aggression. Both had significant improvement in their aggressiveness, and the second patient also improved in the frequency of his seizures and psychotic episodes. The significance of these observations for our understanding of the morphophysiological basis of rage and aggression is discussed.
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Trouillas, Jacqueline, Etienne Delgrange, Anne Wierinckx, Alexandre Vasiljevic, Emmanuel Jouanneau, Pia Burman, and Gerald Raverot. "Clinical, Pathological, and Molecular Factors of Aggressiveness in Lactotroph Tumours." Neuroendocrinology 109, no. 1 (2019): 70–76. http://dx.doi.org/10.1159/000499382.
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The behaviour of lactotroph tumours varies between benign tumours, those cured by treatment, and that of aggressive tumours, and carcinomas with metastasis. Identification of clinical, pathological and molecular factors is essential for the early identification of patients that may have such aggressive tumours. Plasma prolactin levels and tumour size and invasion, per se, are not prognostic factors. However, tumours appearing at a young age (<20 years), especially in boys, and the presence of genetic predisposition have a poorer prognosis. In addition, lactotroph tumours in men differ from those in women, being larger, more often invasive, and resistant to dopamine agonists. They are also more often high-grade with a high risk of recurrence and malignancy. The expression of estrogen receptor α is lower than in women and is closely correlated to aggressiveness. Proliferation markers (Ki-67 expression: ≥3%, mitotic count n > 2) are correlated to invasion and proliferation, but, taken alone, their prognostic value is debatable. Based on a 5-tiered clinicopathological classification, and taking into account invasion and proliferation, a grade 2b (aggressive) lactotroph tumour has a 20× risk of progression compared to a grade 1a (benign) tumour. Moreover, lactotroph tumours are the second-most frequent aggressive and malignant tumour. Other factors, such as the expression of growth factors (vascular endothelial growth factor [VEGF] and epidermal growth factor [EGF]), the genes regulating invasion, differentiation and proliferation, adhesion molecules (E-cadherin), matrix metalloproteinase 9, and chromosome abnormalities (chromosomes 11, 19, and 1), have also been correlated with aggressiveness. Currently, clinical signs, a prognostic classification, and molecular and genetic markers may all help the clinician in the early identification of aggressive lactotroph tumours and enable stratification of their management.
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Dzepina, Davor. "Surgical and Pathological Characteristics of Papillary Thyroid Cancer in Children and Adolescents." International Journal of Pediatrics 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/125389.
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Background. Thyroid carcinoma is a relatively rare pediatric pathology, comprising around 3% of all childhood tumors. We investigated parameters of tumor aggressiveness, multicentricity, and locoregional metastatic spread patterns in patients up to 18 years of age and made comparison with the older group. All patients were operated upon with total thyroidectomy, with or without lymph-node neck dissection.Results. Patients with papillary carcinoma present with more advanced stage, larger primary tumor, and more commonly present with palpable thyroid and/or neck node. Overall, papillary cancer demonstrated pathological aggressiveness as defined by our criteria in 60%, multicentricity in 40%, and locoregional metastatic foci in 77% of cases. Multicentric tumor foci in both thyroid lobes and tumor aggressiveness were identified as a risk factor for metastatic development.Conclusion. By observing clinicopathological parameters, we demonstrated that papillary thyroid cancer behaves more aggressively in the younger group. We recommend total thyroidectomy with careful intraoperative exploration of thyroid bed and lateral neck in search for possible metastatic spread. In case of positive findings, it is obligatory to perform a standard neck dissection, keeping in mind that neck lymphonodes are primary site of locoregional recurrence. With meticulous attention to technical aspects of operation, perioperative morbidity should be minimal.
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Larson, Benjamin T., Cristina Magi-Galluzzi, Graham Casey, Sarah J. Plummer, Robert Silverman, and Eric A. Klein. "Pathological Aggressiveness of Prostatic Carcinomas Related to RNASEL R462Q Allelic Variants." Journal of Urology 179, no. 4 (April 2008): 1344–48. http://dx.doi.org/10.1016/j.juro.2007.11.078.
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Payne Ondracek, Rochelle, Matthew H. Hayn, Michael Adam Poch, Warren Davis, Alexandra Curtis, Hyung Lae Kim, Carl D. Morrison, James Mohler, and James Roger Marshall. "The effect of BMI at time of surgery on long-term outcome after radical prostatectomy." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e15203-e15203. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15203.
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e15203 Background: Body mass index (BMI) at time of surgery was determined among 715 radical prostatectomy patients. The association of BMI with a range of treatment outcomes was considered. Methods: The associations of BMI at time of radical prostatectomy (RP) with disease stage and aggressiveness and long-term outcome were evaluated among 715 patients treated with RP at Roswell Park Cancer Institute between 1993 and 2005. Clinical and pathological aggressiveness indicators included clinical Gleason sum and tumor stage (2002 TNM), highest preoperative PSA, pathological Gleason sum and tumor stage (2002 TNM) and surgical margin status. Ten post-RP recurrence definitions were considered: 1) PSA ≥ 0.2 ng/ml; 2) PSA ≥ 0.4 ng/ml (with 1 confirming value); 3) 1 or more post RP treatments (ADT, radiation, chemotherapy); 4) PSA doubling time < 12 months; 5) PSA doubling time < 9 months; 6) PSA doubling time < 6 months; 7) NCCN definition of PSA failure; 8) AUA definition of PSA failure; 9) diagnosis of metastatic CaP; and 10) death from CaP. Results: Of the 715 men, 33 developed metastatic prostate cancer, and 17 died of prostate cancer. 246 men had BMI ≥ 30. BMI was not significantly associated with clinical or pathological aggressiveness criteria. These analyses showed that there is a trend towards higher risk of the development of metastasis or death for men with BMI ≥ 30, although the association with high BMI and these failure types is not significant. With adjustment for the most significant tumor aggressiveness features (clinical Gleason sum, pathological tumor stage, pathological Gleason sum, and surgical margin status) in proportional hazards regression, men with BMI ≥ 30 had consistently lower risk for all definitions of recurrence except metastasis and death, although no hazard ratios were significant. In contrast, men with higher BMIs had higher risk for metastasis and death from prostate cancer, although neither association is statistically significant. Conclusions: Men with higher BMIs show similar to slightly reduced risk for PSA-based recurrence definitions. Men with higher BMIs had slightly higher risk, though not significant, for metastasis and death. These results seem to support theories that PSA is diluted in men with higher BMIs.
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Cai, Shulei, He Zhang, Xiaojun Chen, Tianping Wang, Jiaqi Lu, Xuefen Liu, and Guofu Zhang. "MR volumetry in predicting the aggressiveness of endometrioid adenocarcinoma: correlation with final pathological results." Acta Radiologica 61, no. 5 (September 29, 2019): 705–13. http://dx.doi.org/10.1177/0284185119877331.
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Background Magnetic resonance (MR) has been widely used in predicting the aggressiveness of endometrioid adenocarcinoma. However, the diagnostic value of the MR volume of the lesion has been controversial. Purpose To determine whether the whole-lesion MR volume measurement could be used as a better predictor for evaluating the aggressiveness of endometrioid adenocarcinoma. Material and Methods In this retrospective study, we include 357 patients with pathologically demonstrated endometrioid adenocarcinoma at our institution between 1 January 2013 and 31 December 2018. Whole-lesion MR volume was calculated on sagittal T2-weighted images with ITK-SNAP software on a personal computer. Results According to the receiver operating characteristics curve analysis, whole-lesion MR volume has the competitive advantage in evaluating deep myometrial invasion compared with the frozen results, generating area under the curve (AUC) values of 0.751 vs. 0.834 ( P = 0.0629, Z = 1.860). The AUC of tumor maximum diameter, simple tumor volume, and whole-lesion MR volume in predicting deep myometrial invasion was 63.8%, 67.6%, and 75.1%, respectively. Conclusion Whole-lesion MR volume is a good diagnostic tool for prediction of deep myometrial invasion, lymph node metastasis, and lymphovascular invasion. MR volumetry could reflect the aggressiveness of endometrioid adenocarcinoma more accurately than traditional lesion measurements.
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Cuello, Gustavo, Gloria I Sánchez, Roberto Jaramillo, Katherine Quintero, Armando Baena, Adriana O’Byrne, Antonio J Reyes, Consuelo Santamaría, Julio C Reina, and Nubia Muñoz. "Clinical characteristics and HPV type in recurrent respiratory papillomatosis in Colombia." Salud Pública de México 55, no. 4 (July 4, 2013): 416. http://dx.doi.org/10.21149/spm.v55i4.7226.
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Objective. Describe factors associated with aggressive forms of recurrent respiratory papillomatosis (RRP). Materials and methods. One hundred eighty-nine RRP cases diagnosed between 1985 and 2009 were identified in pathological records. HPV was detected by the SPF-10 method with broad spectrum primers, (version 1). Results. 113 patients had only one surgery (less aggressive) and 76, two or more interventions (more aggressive). The likelihood of aggressive lesions decreased with increasing age at diagnosis and HPV- 11 was associated with no significant increase in the risk of aggressiveness. Conclusions. The age at diagnosis was the main determinant of RRP aggressiveness.
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Curry, Joseph, David Cognetti, Edmund Pribitkin, Andrew Quong, Colin Wynne, Kathryn Scott, David Rosen, and Elizabeth Duddy. "BRAF Mutation Correlates with Aggressive Features, Little Predictive Value." International Journal of Head and Neck Surgery 5, no. 3 (2014): 130–34. http://dx.doi.org/10.5005/jp-journals-10001-1198.
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ABSTRACT Objective With widespread and sophisticated imaging techniques, micro papillary thyroid cancers (PTCs) may be discovered prior to developing the classic pathological determinants of aggressiveness, such as extrathyroidal extent (ETE). Many studies have suggested that the V600E B-Raf proto-oncogene (BRAF) mutation can be used as a marker for aggressive disease. One objective of this study is to determine what prognostic value this mutation holds. However, nearly all of current studies have focused solely on classically aggressive tumors, not classically nonaggressive samples. This study also seeks to determine the BRAF mutation status in both the groups of tumors. Materials and methods Sixty-six PTC samples were tested for the V600E BRAF mutation using competitive allele-specific TaqMan probes in real-time PCR (Applied Biosystems/Life Technologies). Testing demonstrates that this assay has at least a <5% sensitivity to the mutation. Forty-five samples had at least one of four aggressive features. Samples with vascular invasion, ETE or lymph node metastasis (LNM) were also characterized as having poor prognosis. Results The V600E BRAF mutation was found in 27 of the 45 aggressive samples (60.0%) and 5 of the 21 nonaggressive samples. The Fisher exact test resulted in a correlation between aggressiveness and BRAF mutation as well as correlations between ETE, LNM and the BRAF mutation. When using the BRAF mutation as a predictor of prognosis based on the pathological features of aggressiveness, there was 60% sensitivity and 80% specificity. Conclusion The V600E BRAF mutation is correlated with pathological aggressive features, but may lack sufficient specificity or sensitivity to be used as a marker to predict outcome. How to cite this article Quong A, Wynne C, Curry J, Scott K, Rosen D, Cognetti D, Pribitkin E, Duddy E. BRAF Mutation Correlates with Aggressive Features, Little Predictive Value. Int J Head Neck Surg 2014;5(3):130-134.
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Laruelle, Annick, Claudia Manini, José I. López, and André Rocha. "Early Evolution in Cancer: A Mathematical Support for Pathological and Genomic Evidence in Clear Cell Renal Cell Carcinoma." Cancers 15, no. 24 (December 18, 2023): 5897. http://dx.doi.org/10.3390/cancers15245897.
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Clear cell renal cell carcinoma (CCRCC) is an aggressive form of cancer and a paradigmatic example of intratumor heterogeneity (ITH). The hawk-dove game is a mathematical tool designed to analyze competition in biological systems. Using this game, the study reported here analyzes the early phase of CCRCC development, comparing clonal fitness in homogeneous (linear evolutionary) and highly heterogeneous (branching evolutionary) models. Fitness in the analysis is a measure of tumor aggressiveness. The results show that the fittest clone in a heterogeneous environment is fitter than the clone in a homogeneous context in the early phases of tumor evolution. Early and late periods of tumor evolution in CCRCC are also compared. The study shows the convergence of mathematical, histological, and genomics studies with respect to clonal aggressiveness in different periods of the natural history of CCRCC. Such convergence highlights the importance of multidisciplinary approaches for obtaining a better understanding of the intricacies of cancer.
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Aprasidze, T., and M. Tsirekidze. "Clinico-social Character of Delinquent form of Dissocial (Deviant) Behavior." European Psychiatry 41, S1 (April 2017): S121. http://dx.doi.org/10.1016/j.eurpsy.2017.01.1919.
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IntroductionAmong great variety of the manifestations of juvenile deviation of behavior, with its social significance, delinquency draws a special attention, in particular, with its aggressive manifestation.ObjectivesOur task is specification of psychopathological peculiarities of two forms of aggressive behavior of delinquency.MethodsFifty delinquent juveniles from 14 to 18 years of age (inclusive) have been examined. Two forms of aggressive manifestations have been picked out: non-pathological: 36 (72%) and pathological: 14 (28%).ResultsNon-pathological aggression basically is conditioned by the influence of micro-social negative conditions and stress situations. The contents of aggressive acts are closely connected with the peculiarities of characterological features; aggressive behavior is characterized with an episodic appearing, less severity and is often manifested in threatening. Marked cruelty, sadism and vandalism are found comparatively seldom. The violation of social adaptation is found in them in stresses, stipulated with negative micro-social factors; they are more manageable and comparatively quickly regress.The peculiarities of pathological aggression are represented by super valuable and sadistic manifestations, comparatively seldom–with signs of dysphoria. The aggression, stipulated by pathocharacterological reactions is manifested in the form of pathologically super valued and affective situational acts of behavior.ConclusionsAggressive behavior of delinquency is chiefly observed in its non-pathological form, which can be explained by the hard social-economical background, visible growth of aggressiveness in an immense part of population, moral and ethic deprivation and frustration. The society itself is a certain indicator of aggressiveness.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Rogier, Guyonne, Alessia Marzo, and Patrizia Velotti. "Aggression Among Offenders: The Complex Interplay by Grandiose Narcissism, Spitefulness, and Impulsivity." Criminal Justice and Behavior 46, no. 10 (July 11, 2019): 1475–92. http://dx.doi.org/10.1177/0093854819862013.
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Impulsivity seems closely related to both narcissism and spitefulness as a potential common pathway by which these pathological personality traits lead to violence. We administered the Aggression Questionnaire (AQ), the Pathological Narcissism Inventory, the Spitefulness Scale, and the Impulsive Behavior Scale Short Form to a sample of individuals convicted of violent offenses ( n = 182) and a sample of community participants ( n = 203). Hierarchical regression analysis of the convicted sample showed that spitefulness predicted AQ scores positively and significantly beyond the roles of both pathological narcissism and impulsivity. Finally, mediation analyses showed that impulsivity partially mediated the relationships between aggression and both grandiose narcissism and spitefulness. Our results support the hypothesis that spitefulness plays an important role in the prediction of aggressiveness. Finally, impulsivity seems to be a central common variable that explains the relationship between pathological personality traits and aggressive behavior among individuals convicted of violent offenses.
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Algaba, F. "Renal Adenomas: Pathological Differential Diagnosis with Malignant Tumors." Advances in Urology 2008 (2008): 1–4. http://dx.doi.org/10.1155/2008/974848.
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The renal adenomas can be confused by imaging diagnosis with malignant renal tumors, but there are also real biological dilemmas to determine their behavior. The consensus decisions are the following. (1) The adenoma of clear cells is not accepted, instead it is considered that all the clear-cell tumors are carcinomas, with greater or lesser aggressiveness. (2) Among the papillary neoplasms the WHO 2004 renal cell tumors classification are considered as papillary adenomas tumors with a maximum diameter of 5 mm and may represent a continuum biological process to papillary renal cell carcinoma. The papillary adenomas associated with End-kidney and/or acquired cystic disease may have a different pathogenesis. (3) To consider a tumor as an oncocytoma the size is not important, only the cytological features, microscopic, ultrastructural, and immunohistochemically can help, but some chromosomal observations introduce some questions about its relation with the chromophobe renal cell carcinoma. (4) Finally, the metanephric adenoma, a tumor with some morphological similarity with the nephroblastoma must be considered in the renal adenomas diagnosis.
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Fischer, Tahoun, Klaan, Thierfelder, Weber, Krause, Hakenberg, Fuellen, and Hamed. "A Radiogenomic Approach for Decoding Molecular Mechanisms Underlying Tumor Progression in Prostate Cancer." Cancers 11, no. 9 (September 2, 2019): 1293. http://dx.doi.org/10.3390/cancers11091293.
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Prostate cancer (PCa) is a genetically heterogeneous cancer entity that causes challenges in pre-treatment clinical evaluation, such as the correct identification of the tumor stage. Conventional clinical tests based on digital rectal examination, Prostate-Specific Antigen (PSA) levels, and Gleason score still lack accuracy for stage prediction. We hypothesize that unraveling the molecular mechanisms underlying PCa staging via integrative analysis of multi-OMICs data could significantly improve the prediction accuracy for PCa pathological stages. We present a radiogenomic approach comprising clinical, imaging, and two genomic (gene and miRNA expression) datasets for 298 PCa patients. Comprehensive analysis of gene and miRNA expression profiles for two frequent PCa stages (T2c and T3b) unraveled the molecular characteristics for each stage and the corresponding gene regulatory interaction network that may drive tumor upstaging from T2c to T3b. Furthermore, four biomarkers (ANPEP, mir-217, mir-592, mir-6715b) were found to distinguish between the two PCa stages and were highly correlated (average r = ± 0.75) with corresponding aggressiveness-related imaging features in both tumor stages. When combined with related clinical features, these biomarkers markedly improved the prediction accuracy for the pathological stage. Our prediction model exhibits high potential to yield clinically relevant results for characterizing PCa aggressiveness.
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Poosekeaw, Pirawan, Chawalit Pairojkul, Banchob Sripa, Prakasit Sa Ngiamwibool, Sitthichai Iamsaard, Chadamas Sakonsinsiri, Raynoo Thanan, and Piti Ungarreevittaya. "Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma." PLOS ONE 16, no. 11 (November 15, 2021): e0259075. http://dx.doi.org/10.1371/journal.pone.0259075.
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Cholangiocarcinoma (CCA) is a group of heterogenous malignancies arising from bile duct epithelium with distinct pathological features. Adaptor proteins have implicated in cell proliferation, migration, and invasion of different cancer cells. The objective of this study was to assess whether the adaptor protein XB130 (AFAP1L2) is a critical biological determinant of CCA outcome. XB130 expression levels were investigated in four CCA cell lines compared to an immortalized cholangiocyte cell line by Western blotting. Small interfering (si) RNA-mediated XB130 gene silencing was conducted to evaluate the effects of reduced XB130 expression on cell proliferation, migration, and invasion by MTT, transwell migration and cell invasion assay. The immunohistochemical quantification of XB130 levels were performed in surgically resected formalin-fixed, paraffin-embedded specimens obtained from 151 CCA patients. The relationship between XB130 expression and the clinicopathological parameters of CCA patients were analyzed. Our results showed that XB130 was highly expressed in KKU-213A cell line. Knockdown of XB130 using siRNA significantly decreased the proliferation, migration, and invasion properties of KKU-213A cells through the inhibition of PI3K/Akt pathway, suggesting that XB130 plays an important role in CCA progression. Moreover, elevated XB130 expression levels were positive relationship with lymphovascular space invasion (LVSI), intrahepatic type of CCA, high TNM staging (stage III, IV), high T classification (T3, T4), and lymph node metastasis. We provide the first evidence that the overexpression of XB130 is associated with tumorigenic properties of CCA cells, leading to CCA progression with aggressive clinical outcomes.
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Niechi, Ignacio, Atenea Uribe-Ojeda, José Ignacio Erices, Ángelo Torres, Daniel Uribe, José Dellis Rocha, Pamela Silva, Hans G. Richter, Rody San Martín, and Claudia Quezada. "Adenosine Depletion as A New Strategy to Decrease Glioblastoma Stem-Like Cells Aggressiveness." Cells 8, no. 11 (October 30, 2019): 1353. http://dx.doi.org/10.3390/cells8111353.
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Glioblastoma is the brain tumor with the worst prognosis. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine, which are increased even more under hypoxic conditions. Under hypoxia, adenosine signaling is related to HIF-2α expression, enhancing cell aggressiveness. Adenosine can be degraded using recombinant adenosine deaminase (ADA) to revert its pathological effects. The aim of this study was to degrade adenosine using ADA in order to decrease malignancy of GSCs. Adenosine depletion was performed using recombinant ADA. Migration and invasion were measured by transwell and matrigel-coated transwell assay, respectively. HIF-2α-dependent cell migration/invasion decreased in GSCs treated with ADA under hypoxia. MRPs-mediated chemoresistance and colony formation decreased in treatment with ADA. In conclusion, adenosine depletion using adenosine deaminase decreases GSCs aggressiveness.
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Giusca, Simona Eliza, Elena Corina Andriescu, Irina Draga Caruntu, and Delia Ciobanu. "Clinicopathological Profile of Medullary Thyroid Carcinoma—Could We Predict Aggressive Behavior?" Biomedicines 11, no. 1 (January 3, 2023): 116. http://dx.doi.org/10.3390/biomedicines11010116.
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Medullary thyroid carcinoma (MTC) accounts for only 2–5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims to identify criteria that could predict increased aggressiveness. We analyzed 59 consecutive MTC cases. We focused on the relationships among clinicopathological characteristics, parameters of aggressiveness (extrathyroidal extension, lymphovascular invasion, and lymph node metastasis), and parameters for MTC grading. Statistically significant correlations were found for tumor size, lymphovascular invasion, and lymph node metastasis and tumor focality and lymph node metastasis. Our results showed, in tumors larger than 40 mm, odds ratios (ODs) of 13.695 and 6 for lymphovascular invasion and lymph node metastasis, respectively; in multifocal tumors, we registered an OD of 9.42 for lymph node metastasis. No significant correlation was found for the parameters of the MTC grading system when assessed individually and integrated by reporting low-grade and high-grade risk groups. Although our data indicate that lymphovascular invasion and lymph node metastasis remain significant markers for aggressiveness, studies on larger series of cases are mandatory to detect and validate new factors responsible for the variable course of MTC.
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Bojoga, Andreea, Laura Stănescu, and Corin Badiu. "Collision tumors of the thyroid. A special clinical and pathological entity." Archive of Clinical Cases 8, no. 4 (December 18, 2021): 84–90. http://dx.doi.org/10.22551/2021.33.0804.10191.
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Thyroid collision tumors are rare entities that designate two histologically and morphologically distinct tumors that occur simultaneously or as metastases from other organs within the thyroid. Medullary and papillary carcinoma co-occurrence is the most frequent. Several theories tried to explain the pathogenic mechanisms underlining collision tumors, including the theory which assumes that one tumor predisposes the other, stem cell theory, and random effect theory, but their combination better explains the origin of these tumors. Hypotheses about common genetic behavior responsible for the pathogenesis have also been suggested, such as the involvement of germline mutation of RET (Rearranged during Transfection) proto-oncogene in medullary thyroid carcinoma and papillary thyroid carcinoma coexistence, but there is controversy on this topic. Management of thyroid collision tumors is challenging owing to the presence of two distinct tumors with different biological aggressiveness, treatments options, and prognosis, and needs to be individualized.
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Patnaik, Bhabani, Sumita Tripathy, Inuganti Gopal, and Deepika Sahu. "Clinico-pathological evaluation of gastric adeno carcinoma with reference to ki-67 LI immuno-staining." Panacea Journal of Medical Sciences 13, no. 3 (December 15, 2023): 591–96. http://dx.doi.org/10.18231/j.pjms.2023.109.
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Gastric cancer is a life-threatening disease accounting for the one of the most common types of disease and second most that cause the cancer which lead to death. Many molecular markers were established as a possible prognostic factor apart from routine grading and TNM staging. The variable prognosis of gastric cancer within a pathological grade necessitates a newer marker which can be correlated with the prognosis and aggressiveness of the disease. ki-67 is a nuclear protein that is known as a marker of cellular proliferation and ribosomal RNA transcription. According to analysis, the ki-67 is a nuclear proliferation antigen affecting the health of the people as it cannot be cycle in the resting phase. Moreover, the fraction of ki-67 is clinical course of various cancers. To evaluate the expression of ki-67 LI in gastric cancer and correlate the findings with various clinico-pathological features.Prospective study was conducted from October 2018 to September 2021 at the department of Pathology, MKCG Medical College, Berhampur, Odisha. Two sets of 3–4-micron thickness of tissue sections prepared from blocks of histologically confirmed cases of gastric adenocarcinoma were taken, one for routine H&E and other for ki-67 LI IHC study. IHC protocol of DAKO was followed along with DAB visualisation. The results were correlated with different clinico-pathological features of Gastric cancer. Higher ki-67 LI was correlated significantly with tumour location, histological grade and type but not with age and sex.In our study, IHC assessment of ki-67 LI correlates well with histological grade and type of tumour. ki-67 LI can be taken as a useful method in identifying aggressiveness of the tumour with an indication of adjuvant chemotherapy. Post-operative follow-up and large sample size could throw more light.
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Shah, Remisha Zahid, Samina Qamar, Shahida Niazi, Madiha Ehsan, and Nazia Noor. "Comparison of Breast Cancer Aggressiveness in Young and Older Patients." Pakistan Journal of Medical and Health Sciences 16, no. 5 (May 26, 2022): 335–36. http://dx.doi.org/10.53350/pjmhs22165335.
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Objective: To compare aggressiveness of breast cancer in young and old patients. Study Design: Cross-sectional Place and Duration of Study: Department of Histopathology, King Edward Medical University, Lahore from 1st January 2016 to 31st December 2018. Methodology: One hundred and fifty women were divided into young (<40 years) and adult (>40 years) group depending upon their age. Women with breast cancer within 20-80 years were enrolled. Modified Radical-Mastectomy specimens as well as lumpectomy having axillary-clearance were sent to pathological laboratory. Biopsies were fixed in formalin in addition to hematoxylin, eosin staining. Data was documented and aggressiveness of breast cancer within both groups was evaluated on the basis of factors as tumor size, tumor type, lymph nodes, metastasis, tumor staging and tumor grading. Results: A significant variance in young and adult cases tumor grade, lymph node involvement and tumor size. The young patients had 12.90% cases of metastasis than old only having 4.5% (p<0.05). Similarly high tumor stage and aggressive tumors were also seen in young patients when compared with old. Conclusion: Young patients with breast cancer are more prone towards aggressive carcinoma than older patients. Keywords: Breast cancer. Metastasis, Tumor grade
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Barreira, Joao Vasco, Gil Falcão, Anuraj Parmanande, Ana Sofia Spencer, Diana Simão, Patricia Winckler, and Ricardo Luz. "Prostate cancer in young men: Our experience." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 133. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.133.
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133 Background: Prostate cancer (PCa) diagnosis is not uncommon in younger men. The three recognized risk factors for PCa are increasing age, african-american race and a family history (FH). Data about PCa treatment outcomes are controversial, younger men may have more aggressive disease and worse prognosis. On the other hand, more recent studies suggest higher rates of indolent PCa with more favorable outcomes in young men after radical prostatectomy (RP). We aimed to compare younger (G1, ≤ 55 yo) vs. older adults (G2, > 56 yo) who underwent RP for PCa between 2010-2016 in terms of FH, race and tumor aggressiveness. Secondly, to determine if the PCa in G1 is more aggressive when there is a PCa familiar background. Methods: Between 2010-2016, 419 men underwent RP for clinically localized PCa at Central Lisbon Hospitals, of which 49 were aged ≤55 years at the time of RP. Clinical characteristics such as race, FH, PSA level, clinical stage, and biopsy Gleason score (BGS) were recorded before RP. Pathological parameters (pathological stage, GS and PSA) were collected after surgery. Results: In G1, 31% had PCa FH vs. 10% in G2 (p < 0.001). Before RP, the average PSA in G1 was 7.47 vs. 8.08 in G2 (p = 0.371). In BGS, 44,3% had Gleason (G) 6, 37,4% G7, 6.9% G≥8, not significantly different between both groups (p = 0.651). Albeit, G1 had more aggressive tumors after RP: 27% G6, 45% G7 e 29% G≥8 vs. 37%, 53% e 11% respectively in G2 (p = 0.002). The pathological stage (pT) was not significantly different between groups (p = 0.243). Biochemical recurrence (BCR) was higher in G1 20% vs. 9% (p = 0.010). In a multivariate logistic regression model, the G1 had more BCR (p = 0.047) and higher PCa FH incidence (p = 0.002). When comparing african vs. caucasian men, the first group had more aggressive tumor histology (p = 0.021). Conclusions: Our study demonstrated that the youngest had superior pathological grades with higher BCR rates. Also, we found a strong relationship between G1 and FH of PCa. Data regarding pathological findings after RP in young men are still controversial. Recent studies confirm that pathological PCa characteristics in young men are not more aggressive than in older men. The present intends to add to the scientific debate around the impact of patients’ age in PCa aggressiveness and prognosis.
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Yin, De-tao, Wenxun Wu, Mingchuang Li, Qi-en Wang, Hongqiang Li, Yongfei Wang, Yifeng Tang, and Mingzhao Xing. "DKK3 is a potential tumor suppressor gene in papillary thyroid carcinoma." Endocrine-Related Cancer 20, no. 4 (May 23, 2013): 507–14. http://dx.doi.org/10.1530/erc-13-0053.
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The expression of the Dickkopf homolog 3 (DKK3) gene is downregulated in some human cancers, suggesting a possible tumor suppressor role of this gene. The role and regulation ofDKK3in thyroid cancer have not been examined. In this study, we explored the relationship of promoter methylation with the inactivation ofDKK3and tumor behaviors in papillary thyroid carcinoma (PTC). We used methylation-specific PCR and RT-PCR to examine the promoter methylation and expression ofDKK3and tumor characteristics. We found mRNA expression ofDKK3in 44.9% of the PTC tissue samples vs 100% of the matched normal thyroid tissue samples (P<0.01). In contrast, an opposite distribution pattern ofDKK3gene methylation was observed; specifically, 38.8% of the PTC tissue samples vs 0% of the matched normal thyroid tissue samples harboredDKK3methylation. An inverse correlation between the promoter methylation and mRNA expression ofDKK3in PTC tissue samples was also observed. Moreover, we also found an inverse correlation betweenDKK3expression and some aggressive pathological characteristics of PTC, including high TNM stages and lymph node metastasis, but a positive correlation betweenDKK3promoter hypermethylation and pathological aggressiveness of the tumor. Treatment of the PTC cell line TPC-1 with the demethylating agent 5-azaC reducedDKK3promoter methylation and enhanced its expression, establishing functionally the impact ofDKK3methylation on its expression. Our data thus for the first time demonstrate that theDKK3gene is a potential tumor suppressor gene in thyroid cancer and that aberrant promoter methylation is an important mechanism for its downregulation, which may play a role in the tumorigenesis and aggressiveness of PTC.
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Villalobos-Nova, Karla, María de los Ángeles Toro, Pablo Pérez-Moreno, Ignacio Niechi, and Julio C. Tapia. "The CK2/ECE1c Partnership: An Unveiled Pathway to Aggressiveness in Cancer." Kinases and Phosphatases 2, no. 1 (December 19, 2023): 1–8. http://dx.doi.org/10.3390/kinasesphosphatases2010001.
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The endothelin-1 (ET1) peptide has a pathological role in the activation of proliferation, survival and invasiveness pathways in different cancers. ET1’s effects rely on its activation by the endothelin-converting enzyme-1 (ECE1), which is expressed as four isoforms, differing only in their cytoplasmic N-terminuses. We already demonstrated in colorectal cancer, glioblastoma, and preliminarily lung cancer, that the isoform ECE1c heightens aggressiveness by promoting cancer stem cell traits. This is achieved through a non-canonical ET1-independent mechanism of enhancement of ECE1c’s stability upon CK2-dependent phosphorylation at S18 and S20. Here, a K6 residue is presumably responsible for ECE1c ubiquitination as its mutation to R impairs proteasomal degradation. However, how phosphorylation enhances ECE1c’s stability and how this translates into aggressiveness are still open questions. In this brief report, by swapping residues to either phospho-mimetic or phospho-resistant amino acids, we propose that the N-terminus may also be phosphorylated at Y5 and/or T9 by an unknown kinase(s). In addition, N-terminus phosphorylation may lead to a blockage of K6 ubiquitination, increasing ECE1c’s stability and presumably activating the Wnt/β-catenin signaling pathway. Thus, a novel CK2/ECE1c partnership may be emerging to promote aggressiveness and thus become a biomarker of poor prognosis and a potential therapeutic target for several cancers.
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Zhidkova, Ol'ga. "Prevention of aggressiveness and hostility of police officers with the technology development abilities of emotional-volitional self-regulation." Russian Journal of Deviant Behavior 2, no. 3 (October 31, 2022): 262–76. http://dx.doi.org/10.35750/2713-0622-2022-3-262-276.
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Introduction. Aggressiveness is one of the forms of manifestation of the personality deviations and is differentiated by the degree of intensity from its normal indicators to extreme ones. In the activities of police officers, aggressiveness acts as a defense mechanism, which often exceeds the limits of moderately protective reactions and reaches the level of extreme aggression, manifested as an inadequate response to the exposure of the environmental stimuli. Theoretical analysis of the phenomena of aggressiveness and hostility, as well as the peculiarities of their manifestation in the professional activities of police officers shows the propensity of employees to aggressive and hostile forms of behavior, characterized by stability and stereotypes, determined by both the emotions of fear and formed personality deformities, pathological properties of character. The need for self-control of emotional reactions and lack of competence in assessing the emotional states of others increases the risks of aggressiveness and deviant behavior of police officers and forms a type of destructive personality. For the sphere of professional activity this is a significant obstacle in ensuring its effectiveness and reliability. Prevention of aggressiveness and hostility requires the development and implementation of technology that ensures the development of negative affects regulation skills, emotional states and behavior.
The purpose of the study was to identify the degree of intensity of various indicators of aggressiveness and hostility of police officers, as well as to analyze their changes due to the application of the technology development abilities of emotional-volitional self-regulation.
Methodology, methods and techniques. A complex of empirical and mathematical methods was used in the analysis of changes in the aggression indicators. Empirical data were obtained with the following techniques: the scale of neuropsychic adaptation (J.N. Gurvich), the method «Types of aggressiveness» (L.G. Pochebut), the Cook-Medley Hostility Scale. Data processing was performed using a specialized software package IBM SPSS Statistics 23 and Microsoft Excel. The research used a comparative analysis of empirical data. A group of employees (n=82) with signs of neuropsychic maladaptation of a nonpathological nature was separated from the total sample of subjects (n=253) and divided into an experimental (n=41) and a control group (n=41). In the experimental group, classes were organized for the development of abilities to emotional-volitional self-regulation (forming experiment).
Results and interpretation. A comparative analysis of the values of aggressiveness and hostility of police officers before and after the experiment showed reliable differences for 3 indicators out of 9 (33.33%): self-aggression, total aggressiveness index, and hostility. In the values of the control and experimental groups during the realization of the ascertaining experiment no reliable differences were revealed, after the experiment statistically significant differences in the indicators were found: verbal aggression, emotional aggression, self-aggression, total aggressiveness index, cynicism, aggressiveness, hostility.
Scientific novelty of the study lies in identifying the indicators of aggression and hostility of police officers experiencing states of neuropsychic maladaptation, in clarifying the role of abilities to emotional and volitional self-regulation in the prevention of aggression and hostility, in determining the parameters of changes in the intensity of aggressive and hostile manifestations in the experiment.
Practical Significance. The change in the indicators of aggressiveness and hostility, identified as a result of the forming experiment, indicates the effectiveness of the technology development abilities to emotional and volitional self-regulation and on this basis allows to develop author programs to manage negative emotions and implement the prevention of deviant behavior of police officers.
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Gbande, Pihou, Tawfiq Abukeshek, Fouad Bensari, and Safa El-Kamel. "Pleuropulmonary blastoma, a rare entity in childhood." BJR|case reports 7, no. 4 (July 2021): 20200206. http://dx.doi.org/10.1259/bjrcr.20200206.
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Pleuropulmonary blastoma (PPB) is a rare malignant intrathoracic mesenchymal tumour with a variable aggressiveness. It is the most common primary malignancy in the lung during childhood. In this study, we present a case of a 3-year-old male child who complained of persistent dry cough. Radiographs suggested the diagnosis of PPB, which was been confirmed by the histo-pathological examination of a biopsy taken from the tumour under CT guidance. This case was reported to emphasise the importance of radiology, whether diagnotic or interventional, in diagnosing rare cases such as PPB.
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Silva, Rafaela V. N., Lucas A. Berzotti, Marcella G. Laia, Liliane S. Araújo, Crislaine A. Silva, Karen B. Ribeiro, Millena Brandão, Adilha M. R. Michelleti, Juliana R. Machado, and Régia C. P. Lira. "Implications of MTHFD2 expression in renal cell carcinoma aggressiveness." PLOS ONE 19, no. 2 (February 29, 2024): e0299353. http://dx.doi.org/10.1371/journal.pone.0299353.
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Renal cell carcinoma (RCC) is the most common type of cancer in kidney and is often diagnosed in advanced stages. Until now, there is no reliable biomarker to assess tumor prognosis during histopathological diagnosis. The Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) overexpression has been suggested as prognostic indicator for RCC, however, its protein profile needs to be clarified. This study investigated the MTHFD2 expression in different RCC cohorts, associating it with tumor characteristics and prognostic factors. Gene expression comparisons between non-neoplastic (NN) and tumor samples, as well as patients’ survival analysis, were assessed using KM-Plotter tool. MTHFD2 protein pattern was evaluated in 117 RCC by immunohistochemistry and associations with prognosis, clinical and pathological data were investigated. The tumors exhibited higher MTHFD2 transcript levels than NN, being even higher in the metastatic group. Opposite gene expression patterns were found among clear cell renal cell carcinoma (ccRCC) and pappilary renal cell carcinoma (pRCC) subtypes, showing higher and lower expressions compared to NN samples respectively. Overexpression was associated with shorter overall survival for ccRCC and pRCC subtypes, and shorter recurrence-free survival for pRCC. The immunolabeling profile varied according to tumor subtypes, with lower intensity and expression scores in ccRCC compared to pRCC and to chromophobe renal cell carcinoma (chRCC). MTHFD2 protein expression was associated with larger tumors and higher Fuhrman grades. Although prognostic value of protein immunostaining was not confirmed, patients with higher MTHFD2 tended to have lower survival rates in the pRCC group. The results highlight MTHFD2 different patterns according to RCC histological subtypes, revealing marked variations at both the genetic and protein levels. The mRNA indicated tumor prognosis, and greater expression in the tumor samples. Although MTHFD2 immunolabeling suggests tumor aggressiveness, it needs to be validated in other cohorts as potential prognostic factor.
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Iordanescu, Gheorghe, Charles Brendler, Susan E. Crawford, Alice M. Wyrwicz, Palamadai N. Venkatasubramanian, and Jennifer A. Doll. "MRS measured fatty acid composition of periprostatic adipose tissue correlates with pathological measures of prostate cancer aggressiveness." Journal of Magnetic Resonance Imaging 42, no. 3 (December 19, 2014): 651–57. http://dx.doi.org/10.1002/jmri.24824.
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Barrea, Luigi, Barbara Altieri, Giovanna Muscogiuri, Daniela Laudisio, Giuseppe Annunziata, Annamaria Colao, Antongiulio Faggiano, and Silvia Savastano. "Impact of Nutritional Status on Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) Aggressiveness." Nutrients 10, no. 12 (December 1, 2018): 1854. http://dx.doi.org/10.3390/nu10121854.
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Neuroendocrine tumors (NETs) are rare neoplasms mostly originating from the gastroenteropancreatic tract (GEP-NETs). Data regarding nutritional status in GEP-NET patients are limited. The aim of the study was to investigate the nutritional status and adherence to the Mediterranean Diet (MD) in GEP-NET patients and to correlate them with tumor aggressiveness. A cross-sectional case-control observational study was conducted enrolling 83 patients with well-differentiated G1/G2 GEP-NETs after resection, as well as 83 healthy subjects, age, sex and body mass index-matched. Nutritional status was assessed by evaluating with Bioelectrical Impedance analysis and its phase angle (PhA), adherence to the MD according to PREDIMED score, dietary assessment, anthropometric parameters, and clinico-pathological characteristics. GEP-NET patients consumed less frequently vegetables, fruits, wine, fish/seafood, nuts, and more frequently red/processed meats, butter, cream, margarine, and soda drinks than controls. Patients with more aggressive disease presented a lower adherence to MD according to PREDIMED categories in comparison to G1, localized and free/stable disease status. A smaller PhA value and a lower PREDIMED score were significantly correlated with G2 tumor, metastases, and progressive disease. To the best of our knowledge, this is the first study reporting an association between nutritional status and tumor aggressiveness in a selected group of GEP-NETs. Moreover, higher intakes of food of MD, may represent a potential tool for prevention of tumor aggressiveness. Thus, a skilled nutritionist should be an integral part of the multidisciplinary management of GEP-NET patients.
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Sfoungaristos, Stavros, and P. Perimenis. "Implication of High Grade Intraepithelial Neoplasia in Adverse Pathology after Radical Prostatectomy." Prague Medical Report 113, no. 2 (2012): 156–65. http://dx.doi.org/10.14712/23362936.2015.30.
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The implication of high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer aggressiveness and prognosis is conflicted. The aim of the present study was to evaluate the role of HGPIN in prediction of adverse pathology in patients undergoing a radical prostatectomy. We retrospectively analysed patients who underwent a radical prostatectomy between January 2005 and December 2010. The relationship between HGPIN and the presence of upgrade, positive surgical margins (PSM), extracapsular disease (ECD), seminal vesicle invasion (SVI) and lymph node invasion (LNI) was analysed. HGPIN predictive ability was estimated by using receiver operating characteristic curves. HGPIN was found in 160 (53.3%) specimens. A statistically significant correlation was found between HGPIN and preoperative prostate specific antigen (p=0.020) and patients’ age (p=0.025). No significant differences were found, regarding the presence of adverse pathological findings, between the patients with or without HGPIN, irrespective of the preoperative risk stratification. HGPIN did not reach significance for the prediction of upgrade, PSM, ECD, SVI and LNI. The presence of concomitant HGPIN and prostate cancer found not to be related with tumor aggressiveness in patients undergoing a radical prostatectomy and should not be considered as a parameter for the operative outcome prediction.
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Tran, Nate, Yan Li, Jacob Ellison, Oluwaseun Adegbite, Joanna J. Phillips, Annette Molinaro, Valentina Pedoia, et al. "NIMG-65. IMPROVED SPATIAL MAPPING OF TUMOR AGGRESSIVENESS WITH 1H MAGNETIC RESONANCE SPECTROSCOPY AND DEEP LEARNING IN PATIENTS WITH NEWLY-DIAGNOSED GLIOMA." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii179. http://dx.doi.org/10.1093/neuonc/noac209.683.
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Abstract INTRODUCTION Noninvasive, radiopathomic mapping of tumor aggressiveness can benefit patients with glioma by guiding the selection of tissue samples for diagnosis, increasing extent of resection, and non-invasively characterizing residual tumor burden for subsequent treatment. Although prior studies have demonstrated the utility of metabolic metrics quantified from 1H-MR Spectroscopy (MRS) in probing tumor pathology, this study evaluated the benefit of using the entire 1D-spectrum and deep learning for radiopathomic mapping of intratumoral cellularity, proliferation (ki-67), and a new tumor aggressiveness index (TAI) defined as log((n(ki−67)+n(cellularity))*tumor-score). METHODS Multi-voxel 1H-MRS was acquired on 281 patients newly diagnosed with a glioma (47% IDH-wildtype) immediately before surgical resection. After reconstructing individual spectra at the locations where tissue samples were obtained during surgery and normalizing by NAA in contralateral normal-appearing-white-matter, 607 spectra with corresponding histopathology were deemed of sufficient quality for analysis. A 1D convolutional-neural-network with bidirectional long- and short-term memory deep-learning model using the entire spectrum (0.6-3.6ppm) was compared to mixed-effects regression (with choline-to-NAA index[CNI]) and Random Forest (with CNI+normalized peak heights) models for predicting ki-67, cellularity, and TAI. Results & DISCUSSION Using deep-learning on the entire spectrum resulted in 10.3%-22.1% lower mean absolute error (MAE) and 0.32-0.37 higher R2 values compared to using CNI alone or a random forest model with multiple metabolic metrics. MAE values for all 3 deep-learning models were 26-44% < 1 standard deviation of the ground truth, demonstrating reasonable prediction accuracy within the test data set. Although the lowest MAE (0.16) and highest R2 (0.41) was attained when predicting TAI with deep-learning, the prediction of cellularity resulted in the lowest %MAE. Colormaps of predicted pathology identified regions of heightened aggressiveness surrounding tissue samples with most abnormal pathological features that sometimes extended beyond the non-enhancing lesion. Current work is evaluating the clinical utility of our deep-learning model and predicted maps of aggressiveness.
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Andreasi, Valentina, Stefano Partelli, Marco Manzoni, Francesca Muffatti, Barbara Colombo, Angelo Corti, and Massimo Falconi. "Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET)." Pancreatology 19, no. 1 (January 2019): 57–63. http://dx.doi.org/10.1016/j.pan.2018.11.005.
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Andreasi, Valentina, Stefano Partelli, Marco Manzoni, Francesca Muffatti, Michele Mazza, Barbara Colombo, Angelo Corti, and Massimo Falconi. "Association between preoperative vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET)." Pancreatology 19 (June 2019): S118. http://dx.doi.org/10.1016/j.pan.2019.05.314.
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Chen, H. H., I. H. Chen, C. T. Liao, F. C. Wei, L. Y. Lee, and S. F. Huang. "Preoperative circulating C-reactive protein levels predict pathological aggressiveness in oral squamous cell carcinoma: A retrospective clinical study." Clinical Otolaryngology 36, no. 2 (April 2011): 147–53. http://dx.doi.org/10.1111/j.1749-4486.2011.02274.x.
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Bima, Chiara, Fabio Bioletto, Chiara Lopez, Martina Bollati, Stefano Arata, Matteo Procopio, Iacopo Gesmundo, Ezio Ghigo, Mauro Maccario, and Mirko Parasiliti-Caprino. "Clinical and Pathological Tools for Predicting Recurrence and/or Metastasis in Patients with Pheochromocytoma and Paraganglioma." Biomedicines 10, no. 8 (July 28, 2022): 1813. http://dx.doi.org/10.3390/biomedicines10081813.
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Pheochromocytomas and paragangliomas are endocrine tumors belonging to the family of neural crest cell-derived neoplasms. They have an extremely variable clinical course, characterized by a non-negligible percentage of relapse and/or metastasis after radical surgery. To date, there are no reliable methods to predict the metastatic potential of these neoplasms, despite several clinical, molecular, and histopathological factors that have been extensively studied in the literature as predictors of the recurrence and/or metastasis in these neoplasms with different performances and results. In this review, we aimed to discuss and analyze the most important clinical and histopathological tools for predicting recurrence risk in patients affected by pheochromocytomas or paragangliomas. Thus, we compared the main available predictive models, exploring their applications in stratifying patients’ risks. In conclusion, we underlined the importance of simple and validated tools to better define disease aggressiveness and establish tailored patients’ treatments and follow-ups.
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Malpeli, Giorgio, Federica Filippini, Fabrizio Tedone, Lorena Torroni, Mariella Alloggio, Claudia Castelli, Mariagiulia Dal Cero, et al. "Influence of Tumor Stroma on the Aggressiveness of Poorly Cohesive Gastric Carcinoma." Journal of Personalized Medicine 14, no. 2 (February 9, 2024): 194. http://dx.doi.org/10.3390/jpm14020194.
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Tumor-stroma crosstalk promotes the adaptation of cancer cells to the local microenvironment and sustains their growth. We assessed the quantitative and qualitative impact of intralesional stroma on clinic-pathological features and the prognosis of poorly cohesive gastric cancer (PCGC) variants. Tissue microarrays including 75 PCGC specimens were immunostained for cytokeratin 8/18 and α-smooth muscle actin to assess the relative proportion of neoplastic cells versus stromal components and the cases were subsequently divided into stroma-rich (SR) and stroma-poor (SP) tumors. Stromal status is significantly associated with the depth of tumor invasion. Patient survival rate was found to be higher in the SP compared to the SR tumor group and, hence, abundant stroma was identified as a significant risk factor in univariable analysis but had no independent prognostic impact. We also investigated the mRNA levels of KRT8 and the associated transcriptional signatures using the molecular data of 82 PCGC cases divided into KRT8-high and KRT8-low groups. KRT8-high tumors were enriched in proteins localized in the extracellular compartment and their expression levels correlated with longer survival in the KRT8-high group and shorter overall survival in the KRT8-low group. Comprehensively, we find that relative intralesional stromal content is a marker of aggressiveness in PCGC tumors and that extracellular proteins characterize functionally and clinically different PCGC subgroups.
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Oshi, Masanori, Hideo Takahashi, Yoshihisa Tokumaru, Li Yan, Omar M. Rashid, Masayuki Nagahashi, Ryusei Matsuyama, Itaru Endo, and Kazuaki Takabe. "The E2F Pathway Score as a Predictive Biomarker of Response to Neoadjuvant Therapy in ER+/HER2− Breast Cancer." Cells 9, no. 7 (July 8, 2020): 1643. http://dx.doi.org/10.3390/cells9071643.
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E2F transcription factors play critical roles in the cell cycle. Therefore, their activity is expected to reflect tumor aggressiveness and responsiveness to therapy. We scored 3905 tumors of nine breast cancer cohorts for this activity based on their gene expression for the Hallmark E2F targets gene set. As expected, tumors with a high score had an increased expression of cell proliferation-related genes. A high score was significantly associated with shorter patient survival, greater MKI67 expression, histological grade, stage, and genomic aberrations. Furthermore, metastatic tumors had higher E2F scores than the primary tumors from which they arose. Although tumors with a high score had greater infiltration by both pro- and anti-cancerous immune cells, they had an increased expression of immune checkpoint genes. Estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative cancer with a high E2F score achieved a significantly higher pathological complete response (pCR) rate to neoadjuvant chemotherapy. The E2F score was significantly associated with the expression of cyclin-dependent kinase (CDK)-related genes and strongly correlated with sensitivity to CDK inhibition in cell lines. In conclusion, the E2F score is a marker of breast cancer aggressiveness and predicts the responsiveness of ER-positive/HER2-negative patients to neoadjuvant chemotherapy and possibly to CDK and immune checkpoint inhibitors.
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Koni, Malvina, Isabella Castellano, Emilio Venturelli, Alessandro Sarcinella, Tatiana Lopatina, Cristina Grange, Massimo Cedrino, et al. "Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target." Cancers 14, no. 16 (August 13, 2022): 3918. http://dx.doi.org/10.3390/cancers14163918.
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Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients’ clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases (p = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01–2.2; p = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers (p = 0.017, padj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82–0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.
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Colmenero-Repiso, Ana, María A. Gómez-Muñoz, Ismael Rodríguez-Prieto, Aida Amador-Álvarez, Kai-Oliver Henrich, Diego Pascual-Vaca, Konstantin Okonechnikov, et al. "Identification of VRK1 as a New Neuroblastoma Tumor Progression Marker Regulating Cell Proliferation." Cancers 12, no. 11 (November 20, 2020): 3465. http://dx.doi.org/10.3390/cancers12113465.
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Neuroblastoma (NB) is one of the most common pediatric cancers and presents a poor survival rate in affected children. Current pretreatment risk assessment relies on a few known molecular parameters, like the amplification of the oncogene MYCN. However, a better molecular knowledge about the aggressive progression of the disease is needed to provide new therapeutical targets and prognostic markers and to improve patients’ outcomes. The human protein kinase VRK1 phosphorylates various signaling molecules and transcription factors to regulate cell cycle progression and other processes in physiological and pathological situations. Using neuroblastoma tumor expression data, tissue microarrays from fresh human samples and patient-derived xenografts (PDXs), we have determined that VRK1 kinase expression stratifies patients according to tumor aggressiveness and survival, allowing the identification of patients with worse outcome among intermediate risk. VRK1 associates with cell cycle signaling pathways in NB and its downregulation abrogates cell proliferation in vitro and in vivo. Through the analysis of ChIP-seq and methylation data from NB tumors, we show that VRK1 is a MYCN gene target, however VRK1 correlates with NB aggressiveness independently of MYCN gene amplification, synergizing with the oncogene to drive NB progression. Our study also suggests that VRK1 inhibition may constitute a novel cell-cycle-targeted strategy for anticancer therapy in neuroblastoma.
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Verma, Chandra Prakash, Ankita Singh, and Sunil Choudhary. "Fatal outcome of intracranial embryonal tumor with multiple rosettes: Case report and review of the literature." IP International Journal of Medical Paediatrics and Oncology 8, no. 1 (March 15, 2022): 49–53. http://dx.doi.org/10.18231/j.ijmpo.2022.012.
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There are three known histological variant within the family of embryonal tumor with multiple rosettes. This family included embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). Here we report a case and performed a comprehensive overview in terms of clinical, pathological, molecular and management outcomes of this rare entity of paediatric brain tumor. Clinically these variants found to have similar characteristics like age (<4 year) associated with highly aggressive nature with reported survival period of 2-3 years. In immunohistochemistry (IHC), most commonly applied markers were synaptophysin, neurofilament protein, Neu-N and glial fibrillary acidic protein (GFAP). Recent data on molecular subgroups of PNETs have led to new insights on diagnosis and treatment of these tumors. Subsequently, LIN28A immunoexpression was identified as a highly specific marker for ETMR. As these tumor having poor prognosis because of aggressiveness in nature, treated as high risk brain tumors. Here we want to report a highly aggressiveness nature of disease, a 6 year old child presented with fever, headache and vomiting. Radiological diagnosis suggestive of left parieto-occipital lesion in brain underwent two time surgery and IHC suggestive of embryonal tumors with multilayered rosettes -WHO grade-IV. He had not responded to treatment and died with overall survival of 2 months.
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Fernandez, Eugenia, Luis Ubillos, Nabila Elgul, María Florencia Festari, Daniel Mazal, Otto Pritsch, Isabel Alonso, Eduardo Osinaga, and Nora Berois. "Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer." Cancers 13, no. 22 (November 10, 2021): 5616. http://dx.doi.org/10.3390/cancers13225616.
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Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.
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Zlobec, Inti, Markus Borner, Alessandro Lugli, and Daniel Inderbitzin. "Role of Intra- and Peritumoral Budding in the Interdisciplinary Management of Rectal Cancer Patients." International Journal of Surgical Oncology 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/795945.
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The presence of tumor budding (TuB) at the invasive front of rectal cancers is a valuable indicator of tumor aggressiveness. Tumor buds, typically identified as single cells or small tumor cell clusters detached from the main tumor body, are characterized by loss of cell adhesion, increased migratory, and invasion potential and have been referred to as malignant stem cells. The adverse clinical outcome of patients with a high-grade TuB phenotype has consistently been demonstrated. TuB is a category IIB prognostic factor; it has yet to be investigated in the prospective setting. The value of TuB in oncological and pathological practice goes beyond its use as a simple histomorphological marker of tumor aggressiveness. In this paper, we outline three situations in which the assessment of TuB may have direct implications on treatment within the multidisciplinary management of patients with rectal cancer: (a) patients with TNM stage II (i.e., T3/T4, N0) disease potentially benefitting from adjuvant therapy, (b) patients with early submucosally invasive (T1, sm1-sm3) carcinomas at a high risk of nodal positivity and (c) the role of intratumoral budding assessed in preoperative biopsies as a marker for lymph node and distant metastasis thus potentially aiding the identification of patients suitable for neoadjuvant therapy.
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Mata-Martínez, Esperanza, Adriana Gonzalez-Gallardo, Mauricio Díaz-Muñoz, and Francisco G. Vázquez-Cuevas. "Purinergic Activation of Store-Operated Calcium Entry (SOCE) Regulates Cell Migration in Metastatic Ovarian Cancer Cells." Pharmaceuticals 16, no. 7 (June 29, 2023): 944. http://dx.doi.org/10.3390/ph16070944.
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Store-operated calcium entry (SOCE) is an important process in calcium signaling. Its role in physiological and pathological events is well recognized. However, in cancerous systems, the importance of SOCE in relation to the degree of cancer aggressiveness, as well as its regulation by ligands such as purinergic molecules, are not well documented. This study aimed to characterize a differential effect of the P2Y2 receptor (promoted by UTP of 10 µM and inhibited by ARC118925XX of 1 µM) on intracellular calcium response between metastatic (SKOV-3) and non-metastatic (CAOV-3) ovarian cell lines in conditions of normal (1.5 mM) and zero extracellular calcium concentration. The sustained calcium influx observed exclusively in SKOV-3 cells was associated with the presence of SOCE (promoted by thapsigargin (74.81 ± 0.94 ΔF) and sensitive to 2-APB (20.60 ± 0.85 ΔF)), whereas its absence in CAOV-3 cells (26.2 ± 6.1 ΔF) was correlated with a low expression of ORAI1. The relevance of SOCE in metastatic SKOV-3 cells was further corroborated when 2-APB significantly inhibited (40.4 ± 2.8% of covered area) UTP-induced cell migration (54.6 ± 3.7% of covered area). In conclusion, our data suggest that SOCE activation elicited by the P2Y2 receptor is involved in the aggressiveness of ovarian cancer cells.
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Al-Sarraf, Fatima S., and Issra A. Hussien. "Evaluation of the proliferation marker Ki67 as a prognostic factor in patients with breast carcinoma." Journal of the Faculty of Medicine Baghdad 57, no. 2 (July 1, 2015): 151–55. http://dx.doi.org/10.32007/jfacmedbagdad.572346.
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Background: Breast cancer is the most frequent cancer in women worldwide and in Iraq. Proliferation rates of neoplastic process can be useful in predicting prognosis, aggressiveness of cancers and to guide treatment protocols in clinical practice.Objectives: To evaluate the role of Ki67 as a proliferative marker through analysing the associations between Ki67 with the clinic-pathological parameters, hormone receptors and Her2/neu expression.Patients and methods: Forty paraffin blocks belonging to patient with breast carcinoma and ten blocks with benign diseases were included in this retrospective cross-sectional study and used for the immunohistochemical assessment of hormone receptors, Her2/neu and Ki67.Results: Mean age of the malignant cases was (50.30±9) years; invasive ductal carcinoma was the main histopathological type (87.5%). Three quarters of the cases were with (Grade II) and (T2). Positive lymph node reported in (72.5%) of cases. Malignant cases positively expressed ER, PR, Her2/neu (score 3+) and Ki67 in (75%), (72.5%), (17.5%) and (75%) respectively. Luminal B subtype was the commonest among studied cases.Conclusions: Ki67 proliferative index represented a valuable tool and provided information about aggressiveness and prognosis of breast carcinoma, significant correlations found between Ki67 and tumor grade, lymph node involvement and Her2/neu score.
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Özkan, Arif, Nusret Can Çilesiz, Arif Kalkanli, Cem Tuğrul Gezmiş, and Memduh Aydin. "Could Renal Tumour Scoring Systems Predict Tumour Aggressivity?" Yeni Üroloji Dergisi 18, no. 3 (October 25, 2023): 249–57. http://dx.doi.org/10.33719/yud.2023-18-3-1355748.
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Objective: The aim of this study is to investigate the relationship between R.E.N.A.L. nephrometry score (RNS), Padua score (PS), Centrality (C)-index and tumour aggressivity in T1 renal tumours and to question whether these scoring systems would provide information about the pathology of renal tumours to manage clinical judgement rather than the anatomy of tumour. Material and Methods: We evaluated 83 patients with stage 1 (T1N0M0) clear cell renal cell carcinoma (cRCC) according to preoperative radiological and pathological staging. Patients were divided according to pathological results of cRCC into two groups: Patients with Fuhrman grade 1 or 2 (FG1-2) (Non-aggresive group (NAG)) and patients with FG3-4 and/or TNM Stage 3 (Aggressive group (AG)). RNS, PS and C-index scores were calculated for each patient. Finally,the relationship between nephrometry scores and pathological aggressivity were compared. Results: The mean RNS was calculated as 7.3±2.4. Total RNS was significantly higher in AG (9.2±1.2) than in NAG (6±2.2) (p<0.001). RNS was an independent predictor of pathological aggressive disease (p<0.001). The cut off value of RNS at the highest area under curve was 8 (p<0.001). The mean PS was calculated as 8.1±1.6. PS was also an independent predictor of pathological aggressive disease (p<0.001). The cut off value of PS at the highest area under curve was 8 (p<0.001). The mean C-index score of AG (1.4 ± 0.4) was significantly lower (p<0.001) than NAG (2.7±2.0). C-index is significant in predicting pathological aggressiveness (p<0.001). Conclusions: Our results suggested that higher RNS and PS scores, lower C-index scores were associated with tumour aggressivity of renal tumours.
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Falvo, Laura, Laura Giacomelli, Vito D'Andrea, Antonella Marzullo, Gabriella Guerriero, and Enrico De Antoni. "Prognostic Importance of Sclerosing Variant in Papillary Thyroid Carcinoma." American Surgeon 72, no. 5 (May 2006): 438–44. http://dx.doi.org/10.1177/000313480607200515.
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The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma is known for its high aggressiveness, high incidence of lymph node metastases, and high incidence of pulmonary metastases, and thus its consequently poorer prognosis. In this study, we undertook a retrospective analysis of papillary thyroid carcinomas to assess whether DSV can be considered a predictive factor for prognosis. We performed a retrospective evaluation of the Department's database of patients with papillary thyroid carcinoma who had undergone total thyroidectomy from January 1992 to December 2000. Group I consisted of 83 DSV patients and Group II was 168 pure papillary carcinoma (PC) patients. A significant prevalence of multinodular thyroid disorder on diagnosis was found for PC (P < 0.05), whereas with DSV, there was a significantly higher prevalence of post-thyroiditis nodular thyroid disorder than with PC (P < 0.001). The incidence of laterocervical lymph node pathology on diagnosis was significantly higher for DSV (P < 0.05). In 3.6 per cent of PC patients and 15.7 per cent of DSV patients, we observed recurrences in the regional lymph nodes (P < 0.001). We found 1.2 per cent distant metastases in PC patients and 7.2 per cent in DSV patients (P < 0.05). One PC patient (0.6%) and three DSV patients (3.6%) died of tumor-related causes (P < 0.05). Our study demonstrated that diffuse sclerosing carcinoma leads to a poorer prognosis to the extent that its classification as an autonomous clinical pathological entity is justified. In conclusion, we can state that DSV is a form of papillary thyroid tumor characterized by its higher aggressiveness, diffuse intrathyroid growth, and high incidence of lymph node and pulmonary metastasis. Ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biological aggressiveness, adequate postoperative treatment and close follow-up become essential.
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Almotawa, Fahad, Abdulrahman Alturki, AbdulJabbar AlGhamdi, Mohammed AlEnezi, Naji AlJohani, and Omar Nasser Alhuzaim. "Association Between Body Mass Index and Aggressive Features of Differentiated Thyroid Cancer." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A857. http://dx.doi.org/10.1210/jendso/bvab048.1749.
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Abstract Background: Obesity is recognized as a risk factor for several types of cancers, including differentiated thyroid cancer (DTC). However, the association between obesity and aggressiveness of DTC is controversial. The aim of this study was to assess the relationship between body mass index (BMI), aggressive clinicopathological features of DTC and response to therapy in Saudi population. Methods: We evaluated 209 patients retrospectively who underwent total thyroidectomy at a referral center and diagnosed with DTC. Patients were stratified into 2 groups based on their BMI: non-obese (< 30 kg/m2), and obese (≥ 30 kg/m2). Pathological aggressiveness of DTC as well as clinical outcome were evaluated according to the 2015 American Thyroid Association (ATA) guideline. Data were described as mean ± SD and the categorical data as frequency percent. Mann Whitney test measured the difference in medians of all the metric variables and Chi-square test was applied for the categorical data to measure the intergroup difference between obese and non-obese binary dependent variable. All the inferences were carried out at 95% confidence interval in SPSS 25.0 software. Results: One-hundred twenty (57.4%) of our cohort were obese. Obesity was significantly more common in females (61.7%) than males (29.6%); (p=0.002). There were no differences in histopathological features between the non-obese and obese patients, including tumor size (2.3 ± 1.7 cm vs. 2.5 ± 2.1 cm, respectively, P-value = 0.812), extrathyroidal extension (16.9 % vs. 22.4 %, respectively, P-value=0.336), vascular invasions (25 % vs 18.4 %, respectively, P-value= 0.263) and lymph nodes metastasis (N1a 19.3 % vs 11.6 %, N1b 12.0 % vs. 10.7 % respectively, with P-value = 0.289), were shown between the two groups. In addition, no differences were evident in the ATA risk of recurrence (P-value = 0.843), TNM stage (P-value= 0.797), response to therapy (P-value= 0.252) and survival (P-value= 0.389) across the two groups. Conclusion: No association between BMI and DTC aggressiveness were found in our study population of Saudi patients. In addition, no association were demonstrated between BMI and response to therapy in DTC. These findings suggest that BMI may not be an independent risk factor for aggressiveness in DTC and that other traditional clinicopathological factors should be applied for risk assessment.
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Torres, Cristina V., Rafael G. Sola, Jesús Pastor, Manuel Pedrosa, Marta Navas, Eduardo García-Navarrete, Elena Ezquiaga, and Eduardo García-Camba. "Long-term results of posteromedial hypothalamic deep brain stimulation for patients with resistant aggressiveness." Journal of Neurosurgery 119, no. 2 (August 2013): 277–87. http://dx.doi.org/10.3171/2013.4.jns121639.
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Object Erethism describes severe cases of unprovoked aggressive behavior, usually associated with some degree of mental impairment and gross brain damage. The etiology can be epileptic, postencephalitic, or posttraumatic, or the condition can be caused by brain malformations or perinatal insults. Erethism is often refractory to medication, and patients must often be interned in institutions, where they are managed with major restraining measures. The hypothalamus is a crucial group of nuclei that coordinate behavioral and autonomic responses and play a central role in the control of aggressive behavior. Deep brain stimulation (DBS) of the posteromedial hypothalamus (PMH) has been proposed as a treatment for resistant erethism, although experience with this treatment around the world is scarce. The objective of this study was to examine the long-term outcome of PMH DBS in 6 patients with severe erethism treated at the authors' institution. Methods Medical records of 6 patients treated with PMH DBS for intractable aggressiveness were reviewed. The therapeutic effect on behavior was assessed by the Inventory for Client and Agency Planning preoperatively and at the last follow-up visit. Results Two patients died during the follow-up period due to causes unrelated to the neurosurgical treatment. Five of 6 patients experienced a significant reduction in aggressiveness (the mean Inventory for Client and Agency Planning general aggressiveness score was −47 at baseline and −25 at the last follow-up; mean follow-up 3.5 years). Similar responses were obtained with low- and high-frequency stimulation. In 4 cases, the patients' sleep patterns became more regular, and in 1 case, binge eating and polydipsia ceased. One of the 3 patients who had epilepsy noticed a 30% reduction in seizure frequency. Another patient experienced a marked sympathetic response with high-frequency stimulation during the first stimulation trial, but this subsided when stimulation was set at low frequency. A worsening of a previous headache was noted by 1 patient. There were no other side effects. Conclusions In this case series, 5 of 6 patients with pathological aggressiveness had a reduction of their outbursts of violence after PMH DBS, without significant adverse effects. Prospective controlled studies with a larger number of patients are needed to confirm these results.