scholarly journals Elevated tumor expression of Astroprincin (FAM171A1) is an independent marker of poor prognosis in colon cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tuomas Kaprio ◽  
Alexander M. Lindström ◽  
Tiina Rasila ◽  
Olga Saavalainen ◽  
Ines Beilmann-Lehtonen ◽  
...  

Abstract Background Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. Several biomarkers have been suggested for improved prognostic evaluation, but few have been implemented in clinical practice. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from adjuvant therapy. We recently identified and functionally characterized a previously unknown protein that we called ASTROPRINCIN (APCN) due to its abundance in astrocytes. APCN, also annotated as FAM171A1, is found in trophoblasts of early placenta. We demonstrated that high expression levels of APCN in cancer cells induced motility and ability of invasive growth in semisolid medium. Methods We screened by immunohistochemistry a tissue microarray material from the tumors of 429 CC patients with clinical follow-up in a test series and 255 CC patients in a validation series. Results We showed that low or absent APCN expression correlates with a favorable prognosis while high APCN expression was a sign of an adverse outcome. Cox uni- and multivariable analysis revealed that elevated tumor expression of APCN constitutes a robust marker of poor prognosis independent of stage, grade, patient’s age, or gender. Conclusion Our findings demonstrate that APCN is a novel independent prognostic marker in CC and could potentially select patients for more intense postoperative adjuvant treatment and follow-up.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3619-3619
Author(s):  
M. J. Morris ◽  
B. Iacopetta ◽  
C. Platell

3619 Background: Guidelines for the use of adjuvant chemotherapy in stage II colorectal cancer state this treatment may be considered to patients whose tumours show features of poor prognosis. The aim of the current study was to evaluate the prognostic significance of commonly reported clinical and pathological features of this disease. Methods: A population-based observational study encompassing all stage II colon cancer patients diagnosed in the state of Western Australia from 1993–2003 inclusive. A total of 1306 cases treated by surgery alone were identified and had a median follow-up of 59 months (range 0–145). Results: Multivariate analysis revealed the only independent prognostic factors for disease-specific survival were T4 stage (HR=1.75, 95%CI [1.32–2.32], P<0.0001) and vascular invasion (HR=1.63, 95%CI [1.15–2.30], P<0.0001). In the younger patient group (≤75 yrs) who are more likely to be considered for chemotherapy, the same two features showed independent prognostic significance but with higher HR values (1.96 and 2.73 respectively). T4 and/or the presence of vascular invasion identified a “poor” prognosis group comprising 26% of younger cases and having a 5-year survival rate of 71%. The remaining “good” prognosis group showed 84% survival at 5 years follow-up. Conclusion: This study highlights the importance of accurate pathological assessment of T stage and vascular invasion for the prognostic stratification of stage II colon cancer and their subsequent consideration for adjuvant chemotherapy. No significant financial relationships to disclose.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2520-2520
Author(s):  
Guilherme Fleury Perini ◽  
Luis Villela ◽  
Brady E Beltran ◽  
Denisse Castro ◽  
Victoria Otero ◽  
...  

Abstract Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin America: A cohort of 160 patients from GELL. Introduction: Ongoing SARS-COV-2 pandemic has impacted the management of cancer patients worldwide. Several reports have demonstrated inferior outcomes of patients with hematological malignancies, including higher rates of intensive care unit admission, need for mechanical ventilation and death. The impact of COVID-19 is profound in resource-restricted countries, including Latin America. Most cohorts reported have not included patients from Latin America, and there is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. Grupo de Estudio De Linfoproliferativos En Latino-America (GELL )is a collaborative network of hematological centers in 13 countries in Latin America. We report updated outcomes of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: We conducted a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis We defined active disease as follow: (1) patients with detectable disease either prior to initiating therapy or upon relapse, and/or (2) patients undergoing active cancer treatment. The primary outcome was overall survival at 100 days. Survival curves were estimated using the Kaplan Meier method. Uni and multivariable analysis were carried out with Cox model. Results: A total of 160 patients were available for analysis. Median age was 60 years old. Hypertension was the most common comorbidity (33%). Most patients had aggressive lymphomas (62%), including 43% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas were observed in 13% of patients and Hodgkin lymphoma in 12.5% of patients. With a median follow-up of 37 days, the 100-day OS was 64% (95CI 56-74%, fig. 1). In univariate analysis, age (HR 1.03, p=0.0025), hypertension (HR 2.01, p=0.017), &gt;1 number of prior lines (HR 2.78, p=0.011), patients currently on treatment (HR 1.83, p=0.043), ferritin &gt;2000 ng/mL (HR 4.74 p=0.00047) were associated with inferior OS. In multivariate analysis, age (HR 1.03, p=0.0026) and patients currently on treatment (HR 1.82, p=0.04) had inferior OS. There was a trend towards inferior outcomes in patients receiving monoclonal antibodies in univariate analysis (HR 1.82, p=0.081) but not in multivariable analysis (HR=1.29, p=0.48). Use of steroids was not statistically related to mortality (HR 1.79, p=0.074). Finally, contrary to other cohorts, no improvement in OS was observed in patients diagnosed later on the pandemic (fig. 2). Conclusion: In this large cohort of Latin American patients with lymphoma malignancies, our updated analysis showed a maintained dismal prognosis with COVID-19 infection. With a median follow up of 37 days, the 100-day OS was 64%. Older age and ongoing active cancer treatment were significantly associated with mortality. The use of monoclonal antibodies and systemic corticosteroids were not statistically associated to poor survival. Current efforts are focused on improving immunization in the Latin American population. There is an unmet need for improving survival in patients with hematologic malignancies and COVID-19 infection. Figure 1 Figure 1. Disclosures Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Otero: ASTRA ZENECA: Current Employment. Abello: Dr Reddy's: Research Funding; Amgen: Honoraria; Janssen: Honoraria. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.


2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Ikuma Nozaki ◽  
Yumi Tone ◽  
Junko Yamanaka ◽  
Hideko Uryu ◽  
Yuko Shimizu-Motohashi ◽  
...  

We report about a 14-year-old boy who presented with an anterior mediastinal mass that was diagnosed as malignant teratoma. Surgical resection was performed along with pre- and postoperative chemotherapy. Although elevated alpha-fetoprotein became negative, he experienced pain in his right hip joint 3 months after resection. Systematic evaluation revealed multiple locations of metastasis, and the pathological diagnosis based on bone biopsy was malignant melanoma originating from malignant teratoma, which rapidly progressed. He died 15 months after diagnosis of the original malignant teratoma. Diagnosing and treating malignant transformation of teratoma, including malignant melanoma, is difficult because it is very rare. To our knowledge, this is the second reported case of malignant melanoma arising from a mediastinum malignant teratoma, with both cases having a poor prognosis. In addition to the follow-up of tumor markers, systematic evaluation, including imaging, should be considered even after remission to monitor malignant transformation of teratoma. We expect to establish a successful therapy and improve mortality rate after more such cases are accumulated.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2632
Author(s):  
Aparajita Budithi ◽  
Sumeyye Su ◽  
Arkadz Kirshtein ◽  
Leili Shahriyari

Many colon cancer patients show resistance to their treatments. Therefore, it is important to consider unique characteristic of each tumor to find the best treatment options for each patient. In this study, we develop a data driven mathematical model for interaction between the tumor microenvironment and FOLFIRI drug agents in colon cancer. Patients are divided into five distinct clusters based on their estimated immune cell fractions obtained from their primary tumors’ gene expression data. We then analyze the effects of drugs on cancer cells and immune cells in each group, and we observe different responses to the FOLFIRI drugs between patients in different immune groups. For instance, patients in cluster 3 with the highest T-reg/T-helper ratio respond better to the FOLFIRI treatment, while patients in cluster 2 with the lowest T-reg/T-helper ratio resist the treatment. Moreover, we use ROC curve to validate the model using the tumor status of the patients at their follow up, and the model predicts well for the earlier follow up days.


Author(s):  
Michael A Catalano ◽  
Shahryar G Saba ◽  
Bruce Rutkin ◽  
Greg Maurer ◽  
Jacinda Berg ◽  
...  

Abstract Aims Up to 40% of patients with aortic stenosis (AS) present with discordant grading of AS severity based on common transthoracic echocardiography (TTE) measures. Our aim was to evaluate the utility of TTE and multi-detector computed tomography (MDCT) measures in predicting symptomatic improvement in patients with AS undergoing transcatheter aortic valve replacement (TAVR). Methods and results A retrospective review of 201 TAVR patients from January 2017 to November 2018 was performed. Pre- and post-intervention quality-of-life was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Pre-intervention measures including dimensionless index (DI), stroke volume index (SVI), mean transaortic gradient, peak transaortic velocity, indexed aortic valve area (AVA), aortic valve calcium score, and AVA based on hybrid MDCT-Doppler calculations were obtained and correlated with change in KCCQ-12 at 30-day follow-up. Among the 201 patients studied, median KCCQ-12 improved from 54.2 pre-intervention to 85.9 post-intervention. In multivariable analysis, patients with a mean gradient &gt;40 mmHg experienced significantly greater improvement in KCCQ-12 at follow-up than those with mean gradient ≤40 mmHg (28.1 vs. 16.4, P = 0.015). Patients with MDCT-Doppler-calculated AVA of ≤1.2 cm2 had greater improvements in KCCQ-12 scores than those with computed tomography-measured AVA of &gt;1.2 cm2 (23.4 vs. 14.1, P = 0.049) on univariate but not multivariable analysis. No association was detected between DI, SVI, peak velocity, calcium score, or AVA index and change in KCCQ-12. Conclusion Mean transaortic gradient is predictive of improvement in quality-of-life after TAVR. This measure of AS severity may warrant greater relative consideration when selecting the appropriateness of patients for TAVR.


2021 ◽  
Vol 10 (13) ◽  
pp. 2927
Author(s):  
Amaar Obaid Hassan ◽  
Gregory Y. H. Lip ◽  
Arnaud Bisson ◽  
Julien Herbert ◽  
Alexandre Bodin ◽  
...  

There are limited data on the relationship of acute dental infections with hospitalisation and new-onset atrial fibrillation (AF). This study aimed to assess the relationship between acute periapical abscess and incident AF. This was a retrospective cohort study from a French national database of patients hospitalized in 2013 (3.4 million patients) with at least five years of follow up. In total, 3,056,291 adults (55.1% female) required hospital admission in French hospitals in 2013 while not having a history of AF. Of 4693 patients classified as having dental periapical abscess, 435 (9.27%) developed AF, compared to 326,241 (10.69%) without dental periapical abscess that developed AF over a mean follow-up of 4.8 ± 1.7 years. Multivariable analysis indicated that dental periapical abscess acted as an independent predictor for new onset AF (p < 0.01). The CHA2DS2VASc score in patients with acute dental periapical abscess had moderate predictive value for development of AF, with Area Under the Curve (AUC) 0.73 (95% CI, 0.71–0.76). An increased risk of new onset AF was identified for individuals hospitalized with dental periapical abscess. Careful follow up of patients with severe, acute dental periapical infections is needed for incident AF, as well as investigations of possible mechanisms linking these conditions.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Henderikus E. Boersma ◽  
Robert P. van Waateringe ◽  
Melanie M. van der Klauw ◽  
Reindert Graaff ◽  
Andrew D. Paterson ◽  
...  

Abstract Background Skin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may predict the development of CVD and mortality in individuals with T2D. Methods We included 2349 people with T2D, available baseline SAF measurements (measured with the AGE reader) and follow-up data from the Lifelines Cohort Study. Of them, 2071 had no clinical CVD at baseline. 60% were already diagnosed with diabetes (median duration 5, IQR 2–9 years), while 40% were detected during the baseline examination by elevated fasting blood glucose ≥7.0 mmol/l) and/or HbA1c ≥6.5% (48 mmol/mol). Results Mean (±SD) age was 57 ± 12 yrs., BMI 30.2 ± 5.4 kg/m2. 11% of participants with known T2D were treated with diet, the others used oral glucose-lowering medication, with or without insulin; 6% was using insulin alone. Participants with known T2D had higher SAF than those with newly-detected T2D (SAF Z-score 0.56 ± 0.99 vs 0.34 ± 0.89 AU, p < 0.001), which reflects a longer duration of hyperglycaemia in the former group. Participants with existing CVD and T2D had the highest SAF Z-score: 0.78 ± 1.25 AU. During a median follow-up of 3.7 yrs., 195 (7.6%) developed an atherosclerotic CVD event, while 137 (5.4%) died. SAF was strongly associated with the combined outcome of a new CVD event or mortality (OR 2.59, 95% CI 2.10–3.20, p < 0.001), as well as incidence of CVD (OR 2.05, 95% CI 1.61–2.61, p < 0.001) and death (OR 2.98, 2.25–3.94, p < 0.001) as a single outcome. In multivariable analysis for the combined endpoint, SAF retained its significance when sex, systolic blood pressure, HbA1c, total cholesterol, eGFR, as well as antihypertensive and statin medication were included. In a similar multivariable model, SAF was independently associated with mortality as a single outcome, but not with incident CVD. Conclusions Measuring SAF can assist in prediction of incident cardiovascular disease and mortality in individuals with T2D. SAF showed a stronger association with future CVD events and mortality than cholesterol or blood pressure levels.


Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001496
Author(s):  
Tiffany Patterson ◽  
Harriet Hurrell ◽  
Jack Lee ◽  
Giulia Esposito ◽  
Utkarsh Dutta ◽  
...  

AimsDurability of transcatheter aortic valve implantation (TAVI) is key to its expansion. We sought to identify incidence of valve thrombosis and predictors of valve thrombosis in our single centre with associated coagulation testing pre-TAVI and post-TAVI.Methods and resultsThis single-centre observational study comprised patients undergoing transfemoral TAVI discussed in the Heart Team meeting . Patients were followed up with echocardiography at 120 days to identify incidence of elevated transvalvular gradient and multivariable analysis was performed to identify factors associated with an increased odds of developing valve thrombosis. In addition, 11 patients underwent baseline, day 1 and day 120 post-TAVI coagulation testing. Between August 2017 and August 2019, 437 consecutive patients underwent transfemoral TAVI. Of these patients, 207/437 (47.4%) had 3-month follow-up echo data available and were analysed. Of these patients, 26/207 (12.6%) had elevated transvalvular gradients. These patients tended to be younger (80±14 vs 83±6 years; p=0.047) with a lower ejection fraction (49±13 vs 54%±11%; p=0.021), with a greater proportion of the population experiencing atrial fibrillation (14/21, 54% vs 68/181, 38%; p=0.067). Following multivariable analysis, there remained a trend towards higher eccentricity index associated with elevated gradients. Baseline (pre-TAVI) elevation of thrombin antithrombin levels (56±63; reference range 1.0–4.1 ng/L) and PF 1+2 (791±632; reference range 69–229 ng/mL) normalised at 120 days post-TAVIConclusionThis study demonstrated that in the cohort of patients undergoing transfemoral TAVI in our centre: younger age, poor ejection fraction, atrial fibrillation and increased baseline eccentricity of the aortic valve annulus were present to a greater extent in patients exhibiting elevated transvalvular gradients at 3-month follow-up. Further work is required to delineate the extent of coagulation derangement and confirm predictors of thrombosis.


2021 ◽  
Vol 12 (3) ◽  
pp. 367-374
Author(s):  
Mohamed F. Elsisy ◽  
Joseph A. Dearani ◽  
Elena Ashikhmina ◽  
Prasad Krishnan ◽  
Jason H. Anderson ◽  
...  

Objective: To identify risk factors for pediatric mechanical mitral valve replacement (mMVR) to improve management in this challenging population. Methods: From 1993 to 2019, 93 children underwent 119 mMVR operations (median age, 8.8 years [interquartile range [IQR]: 2.1-13.3], 54.6% females) at our institution. Twenty-six (21.8%) patients underwent mMVR at ≤2 years and 93 (78.2%) patients underwent mMVR at >2 years. Median follow-up duration was 7.6 years [IQR: 3.2-12.4]. Results: Early mortality was 9.7%, but decreased with time and was 0% in the most recent era (13.9% from 1993 to 2000, 7.3% from 2001 to 2010, 0% from 2011 to 2019, P = .04). It was higher in patients ≤2 years compared to patients >2 years (26.9% vs 2.2%, P < .01). On multivariable analysis for mitral valve reoperation, valve size <23 mm was significant with a hazard ratio of 5.38 (4.87-19.47, P = .01);. Perioperative stroke occurred in 1% and permanent pacemaker was necessary in 12%. Freedom from mitral valve reoperation was higher in patients >2 years and those with a prosthesis ≥23 mm. Median time to reoperation was 7 years (IQR: 4.5-9.1) in patients >2 years and 3.5 years (IQR: 0.6-7.1) in patients ≤2 years ( P = .0511), but was similar between prosthesis sizes ( P = .6). During follow-up period (median 7.6 years [IQR: 3.2-12.4], stroke occurred in 10%, prosthetic valve thrombosis requiring reoperation in 4%, endocarditis in 3%, and bleeding in 1%. Conclusion: Early and late outcomes of mMVR in children are improved when performed at age >2 years and with prosthesis size ≥23 mm. These factors should be considered in the timing of mMVR.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii185-ii185
Author(s):  
Conrad Josef Villafuerte ◽  
Fred Gentili ◽  
David Shultz ◽  
Alejandro Berlin ◽  
Robert Heaton ◽  
...  

Abstract INTRODUCTION The effect of stereotactic radiosurgery (SRS) dose-rate on tumor control for acoustic neuroma (AN, or vestibular schwannoma) is unclear. METHODS This was a retrospective study of all patients treated for AN with frame-based cobalt-60 SRS at the Toronto Western Hospital between 2005-2019. Dose rates on the day of SRS were calculated from the calibration dose-rate while accounting for the cobalt-60 half-life of 5.2713 years. Local failure was defined as continued tumor growth &gt;36 months post-SRS, tumor resection for LF, or use of any repeat SRS for LF. Cumulative incidence of LF was reported after accounting for competing risks of death, on a per-lesion basis. Comparisons of actuarial LF were made using Gray’s test. Multivariable analysis of LF was performed using a proportional hazards model. RESULTS A total of 607 patients were treated for 617 acoustic neuromas. Median follow-up was 5.0 years. 158 tumors (26%) were cystic. 71 tumors (12%) had previous resection. Nine patients received 10-11 Gy due to large tumor size; all remaining patients received 12 Gy to approximately the 50% isodose line. Median dose rate was 2.4 Gy/min (range, 1.3-3.7). There was no association between dose rate and LF (≥ 2.4 Gy/min vs. &lt; 2.4 Gy/min, 6.07% vs. 6.12% at 5-year follow-up, p = 0.75). The adjusted local failure-specific hazard ratio (HR) for dose rate (per Gy/min) was 1.2 (95% CI 0.69-2.1, p = 0.52). Patients with previous surgery had higher LF, with a HR of 3.6 (95% CI 1.7-7.8, p = 0.0012), after adjusting for presence of cysts (HR 0.27, p = 0.034) and maximum tumor diameter (HR 1.055 per cm, p = 0.071). CONCLUSIONS In a large cohort of patients with acoustic neuromas, radiosurgery dose-rate was not associated with tumor control. Previous resection was a strong risk factor for local failure after SRS.


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