Survival in small choroidal melanocytic lesions with risk factors managed by initial observation until detection of tumour growth

In glabrous skin, nevi and melanomas exhibit pigmented stripes during clinical dermoscopic examination. They find their origin in the basal layer geometry which periodically exhibits ridges, alternatively large (limiting ridges) and thin (intermediate ridges). However, nevus and melanoma lesions differ by the localization of the pigmented stripes along furrows or ridges of the epidermis surface. Here, we propose a biomechanical model of avascular tumour growth which takes into account this specific geometry in the epidermis where both kinds of lesions first appear. Simulations show a periodic distribution of tumour cells inside the lesion, with a global contour stretched out along the ridges. In order to be as close as possible to clinical observations, we also consider the melanin transport by the keratinocytes. Our simulations show that reasonable assumptions on melanocytic cell repartition in the ridges favour the limiting ridges of the basal compared with the intermediate ones in agreement with nevus observations but not really with melanomas. It raises the question of cell aggregation and repartition of melanocytic cells in acral melanomas and requires further biological studies of these cells in situ .

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Genomic classifier to augment the role of pathological features in identifying optimal candidates for adjuvant radiation therapy in patients with prostate cancer: Development and internal validation of a multivariable prognostic model.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.142 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 142-142

Author(s):

Firas Abdollah ◽

Deepansh Dalela ◽

Maria Santiago-Jimenez ◽

Kasra Yousefi ◽

Jeffrey Karnes ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Risk Stratification ◽

Cox Regression ◽

Adjuvant Radiation ◽

Cumulative Number ◽

Clinical Recurrence ◽

Cox Regression Analysis ◽

Initial Observation ◽

Risk Stratification Tool

142 Background: Despite documented oncological benefit, postoperative adjuvant radiotherapy (aRT) utilization in prostate cancer (PCa) patients is still limited in the US. We aimed to develop and internally validate a risk stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Methods: Our cohort included a total of 512 PCa patients treated with RP at one of four US academic centers between 1990-2010. All patients had ≥ pT3a disease, positive margins, and/or pathologic lymph node invasion (LNI). Multivariable Cox regression analysis (MVA) tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk stratification tool. Our study adhered to the TRIPOD guidelines for development of prognostic models. Results: Overall, 21.9% patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT vs. initial observation (p < 0.001). Pathological T3b/T4 stage, Gleason score 8-10, LNI and Decipher score > 0.6 were independent predictors of CR (all p < 0.01) Cumulative number of risk factors was 0, 1, 2, and 3-4 in respectively 46.5, 28.9, 17.2, and 7.4% of patients. Adjuvant RT was associated with decreased CR rate in patients with ≥ 2 risk factors (10-year CR rate 10.1% in aRT vs. 42.1% in initial observation, p = 0.008), but not in those with < 2 risk factors (p = 0.23). Conclusions: Utilizing the novel model to indicate aRT might reduce overtreatment, decrease unnecessary side effects, and reduce risk of CR in the subset of patients (~25% of all patients with aggressive pathological disease) who really benefit from this therapy.

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Correction: Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs

PLoS ONE ◽

10.1371/journal.pone.0163189 ◽

2016 ◽

Vol 11 (9) ◽

pp. e0163189

Author(s):

Renáta Zsanett Csoma ◽

Edit Tóth-Molnár ◽

Anita Varga ◽

Hajnalka Szabó ◽

Hajnalka Orvos ◽

...

Keyword(s):

Risk Factors ◽

Dizygotic Twin ◽

Melanocytic Lesions ◽

Relationship Of

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Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model

Journal of Clinical Oncology ◽

10.1200/jco.2016.69.9918 ◽

2017 ◽

Vol 35 (18) ◽

pp. 1982-1990 ◽

Cited By ~ 42

Author(s):

Deepansh Dalela ◽

María Santiago-Jiménez ◽

Kasra Yousefi ◽

R. Jeffrey Karnes ◽

Ashley E. Ross ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Lymph Node ◽

Risk Stratification ◽

The United States ◽

Cumulative Number ◽

Clinical Recurrence ◽

Cox Regression Analysis ◽

Initial Observation ◽

Risk Stratification Tool

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P < .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score > 0.6 were independent predictors of CR (all P < .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy.

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Risk factors for metastasis of small choroidal melanocytic lesions. Are we waiting too long?

American Journal of Ophthalmology ◽

10.1016/s0002-9394(14)70559-8 ◽

1996 ◽

Vol 121 (1) ◽

pp. 109

Author(s):

CL Shields ◽

JA Shields ◽

H Kiratli ◽

JR Cater

Keyword(s):

Risk Factors ◽

Melanocytic Lesions

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Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in Monozygotic and Dizygotic Twin Pairs

PLoS ONE ◽

10.1371/journal.pone.0160146 ◽

2016 ◽

Vol 11 (8) ◽

pp. e0160146 ◽

Cited By ~ 4

Author(s):

Renáta Zsanett Csoma ◽

Edit Tóth-Molnár ◽

Anita Varga ◽

Hajnalka Szabó ◽

Hajnalka Orvos ◽

...

Keyword(s):

Risk Factors ◽

Dizygotic Twin ◽

Melanocytic Lesions ◽

Relationship Of

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Risk Factors for Progression Among Low-Grade Gliomas After Gross Total Resection and Initial Observation in the Molecular Era

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.04.010 ◽

2019 ◽

Vol 104 (5) ◽

pp. 1099-1105 ◽

Cited By ~ 4

Author(s):

Martin C. Tom ◽

Vamsi Varra ◽

C. Marc Leyrer ◽

Deborah Y. Park ◽

Samuel T. Chao ◽

...

Keyword(s):

Risk Factors ◽

Gross Total Resection ◽

Low Grade ◽

Total Resection ◽

Low Grade Gliomas ◽

Initial Observation

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Risk Factors for Growth and Metastasis of Small Choroidal Melanocytic Lesions

Ophthalmology ◽

10.1016/s0161-6420(95)30864-0 ◽

1995 ◽

Vol 102 (9) ◽

pp. 1351-1361 ◽

Cited By ~ 156

Author(s):

Carol L. Shields ◽

Jerry A. Shields ◽

Hayyam Kiratli ◽

Patrick De Potter ◽

Jacqueline R. Cater

Keyword(s):

Risk Factors ◽

Melanocytic Lesions

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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