scholarly journals Benign Tumors in Long-Term Survivors of Retinoblastoma

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1773
Author(s):  
Milo van Hoefen Wijsard ◽  
Sara J. Schonfeld ◽  
Flora E. van Leeuwen ◽  
Annette C. Moll ◽  
Armida W. Fabius ◽  
...  

Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.e., bilateral retinoblastoma or unilateral with family history, mutation testing was not available) and 924 nonhereditary retinoblastoma survivors diagnosed during 1914–2006 at two US medical centers with follow-up through 2016. Using Cox proportional hazards regression, we compared benign tumor risk by hereditary status and evaluated the association between benign tumors and SMNs. There were 100 benign tumors among 73 hereditary survivors (cumulative incidence = 17.6%; 95% confidence interval [CI] = 12.9–22.8%) and 22 benign tumors among 16 nonhereditary survivors (cumulative incidence = 3.9%; 95%CI = 2.2–6.4%), corresponding to 4.9-fold (95%CI = 2.8–8.4) increased risk for hereditary survivors. The cumulative incidence after hereditary retinoblastoma was highest for lipoma among males (14.0%; 95%CI = 7.7–22.1%) and leiomyoma among females (8.9%; 95%CI = 5.2–13.8%). Among hereditary survivors, having a prior SMN was associated with 3.5-fold (95%CI = 2.0–6.1) increased risk of developing a benign tumor; the reciprocal risk for developing an SMN after a benign tumor was 1.8 (95%CI = 1.1–2.9). These large-scale, long-term data demonstrate an increased risk for benign tumors after hereditary versus nonhereditary retinoblastoma. If confirmed, the association between benign tumors and SMNs among hereditary patients may have implications for long-term surveillance.

2014 ◽  
Vol 32 (29) ◽  
pp. 3284-3290 ◽  
Author(s):  
Jeannette R. Wong ◽  
Lindsay M. Morton ◽  
Margaret A. Tucker ◽  
David H. Abramson ◽  
Johanna M. Seddon ◽  
...  

Purpose Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks. Patients and Methods In a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale. Results Nearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) –containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio [HR], 1.27; 95% CI, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% CI, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% CI, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% CI, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% CI, 1.76 to 15.17) but not for those receiving AAs at age ≥ 1 year (HR, 1.75; 95% CI, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P = .01). Conclusion This comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rebecca R Hartog ◽  
Kimberly J Watkins ◽  
Megan Wilde ◽  
Tiffany R Lim ◽  
Andrew Rodenbarger ◽  
...  

Introduction: Limited data exist on the electrophysiologic outcomes of patients undergoing anatomic repair (AR) for congenitally corrected transposition of the great arteries (ccTGA). AR was defined as an atrial switch procedure plus either arterial switch (ASO) or Rastelli operation. Aims: To report mid and late electrophysiologic outcomes after AR and identify risk factors for those outcomes. Methods: Single center retrospective cohort study of patients undergoing AR between 1993-2017. Data were collected from available records. Transplant-free survival to 1 year post repair was required for inclusion. Standard descriptive statistical analysis and Cox proportional hazards were used. Results: Of 85 patients included, 95% had lesions in addition to ccTGA: most commonly VSD (84%) and pulmonary stenosis or atresia (58%). Median age at AR was 1.5y (IQR 0.9-2.8) with Senning/ASO in 56%, Senning/Rastelli in 38%, and hemi-Senning/Glenn/Rastelli in 6%. During a median follow-up of 10.6y, 45 (53%) patients developed an arrhythmia requiring intervention. Atrial tachycardia (AT) in 27 (32%) or ventricular tachycardia (VT) in 11 (13%) patients required intervention at a median of 7.4y (IQR 1.6-15.3y) and 15.9y (IQR 4.5-17.9) post-AR, respectively. Treatments included chronic medications in 29 (64%), cardioversion in 15 (33%) and catheter ablation in 10 (22%). Median freedom from AT and VT was 17.3y and 25y post-AR, respectively. D-looped ventricles (p=0.03) and multiple operations prior to AR (p=0.02) were associated with increased AT risk; and native pulmonary stenosis with increased VT risk (p=0.01). Those needing heart failure/transplant referral had increased risk of both AT and VT (both p=0.04). Pacemaker was implanted for heart block and/or SND prior to or during AR in 14 (16%), immediately post-op in 9 (11%), and late (median 6y post-AR) in 24 (28%). ICDs were implanted in 5 (6% of cohort), 4 for primary prevention. No patient had an appropriate shock. Conclusions: Anatomic ccTGA repair is associated with significant electrophysiologic morbidity. AT, VT, and SND develop at a similar incidence to that reported for d-TGA patients after atrial switch. The incidence of AV block follows a similar trajectory to that of physiologically palliated ccTGA.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10051-10051
Author(s):  
Danielle Novetsky Friedman ◽  
Pamela J Goodman ◽  
Wendy Leisenring ◽  
Lisa Diller ◽  
Susan Lerner Cohn ◽  
...  

10051 Background: Infants with neuroblastoma typically have low-risk disease with excellent survival. Therapy has been de-intensified over time to minimize late effects, however the impact on survivors’ risk of late mortality, subsequent malignant neoplasms (SMN), and chronic health conditions (CHC) is unclear. Methods: We evaluated late mortality, SMNs and CHCs (graded according to CTCAE v4.03), overall and by diagnosis era, among 990 5-year neuroblastoma survivors diagnosed at < 1 year of age between 1970-1999. Cumulative mortality, standardized mortality ratios (SMR), and standardized incidence ratios (SIR) of SMNs were estimated using the National Death Index and SEER rates, respectively. Cox proportional hazards estimated hazard ratios (HR) and 95% confidence intervals (CI) for CHC, compared to 5,051 CCSS siblings. Results: Among survivors (48% female; median attained age: 24 years, range 6-46), there was increased treatment with surgery alone across the 1970s, 1980s and 1990s (21.5%, 35.3%, 41.1%, respectively), but decreased treatment with combination surgery + radiation (22.5%, 5.3%, 0.3%, respectively) and surgery + radiation + chemotherapy (28.7%, 14.7%, 9.3%, respectively). The 20-year cumulative mortality was 2.3% (95% CI, 1.4-3.8), primarily due to SMNs (SMRSMN= 10.0, 95% CI, 4.5-22.3). The 20-year cumulative incidence of SMN was 1.2% (95% CI, 0.3-3.2), 2.5% (95% CI, 1.3-4.4), and zero for those diagnosed in the 1970s, 1980s, and 1990s, respectively. SIR was highest for renal SMNs (SIR 12.5, 95% CI, 1.7-89.4). Compared to siblings, survivors were at increased risk for grade 1-5 CHC (HR 2.1, 95% CI, 1.9-2.3) with similar HR across eras (HR1970s= 1.9, 95% CI, 1.6-2.2; HR1980s= 2.2, 95% CI, 1.9-2.6; HR1990s= 2.0, 95% CI, 1.7-2.4). The HR of severe, disabling, life-threatening and fatal CHC (grades 3-5) decreased in more recent eras (HR1970s= 4.7, 95% CI, 3.4-6.6; HR1980s= 4.4, 95% CI, 3.2-6.2; HR1990s= 2.9, 95% CI, 2.0-4.3). Conclusions: Survivors of infant neuroblastoma remain at increased risk for late mortality, SMN, and CHCs many years after diagnosis. However, the risk of grade 3-5 CHCs has declined in more recent eras, likely reflecting de-intensification of therapy.


2005 ◽  
Vol 23 (34) ◽  
pp. 8597-8605 ◽  
Author(s):  
John J. Doyle ◽  
Alfred I. Neugut ◽  
Judith S. Jacobson ◽  
Victor R. Grann ◽  
Dawn L. Hershman

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.


2020 ◽  
Author(s):  
Yingting Zuo ◽  
Anxin Wang ◽  
Shuohua Chen ◽  
Xue Tian ◽  
Shouling Wu ◽  
...  

Abstract Background The relationship between estimated glomerular filtration rate (eGFR) trajectories and myocardial infarction (MI) remains unclear in people with diabetes or prediabetes. We aimed to identify common eGFR trajectories in people with diabetes or prediabetes and to examine their association with MI risk. Methods The data of this analysis was derived from the Kailuan study, which was a prospective community-based cohort study. The eGFR trajectories of 24,723 participants from year 2006 to 2012 were generated by latent mixture modeling. Incident cases of MI occurred during 2012 to 2017, confirmed by review of medical records. Cox proportional hazards models were used to calculate hazard ratios (HR) and their 95% confidence intervals (CIs) for the subsequent risk of MI of different eGFR trajectories. Results We identified 5 distinct eGFR trajectories, and named them as low-stable (9.4%), moderate-stable (31.4%), moderate-increasing (29.5%), high-decreasing (13.9%) and high-stable (15.8%) according to their range and pattern. During a mean follow-up of 4.61 years, there were a total of 235 incident MI. Although, the high-decreasing group had similar eGFR levels with the moderate-stable group at last exposure period, the risk was much higher (adjusted HR, 3.43; 95%CI, 1.56–7.54 versus adjusted HR, 2.82; 95%CI, 1.34–5.95). Notably, the moderate-increasing group had reached to the normal range, still had a significantly increased risk (adjusted HR, 2.55; 95%CI, 1.21–5.39). Conclusions eGFR trajectories were associated with MI risk in people with diabetes or prediabetes. Emphasis should be placed on early and long-term detection and control of eGFR decreases to further reduce MI risk.


2021 ◽  
Author(s):  
Jae Hyun Park ◽  
Hyun Seok Cho ◽  
Gilseong Moon ◽  
Jong Ho Yoon

Abstract Background The rapidly increasing coincidence of thyroid cancer and metabolic syndrome (MS) in recent decades suggests an association between the two disorders. To investigate this association, we conducted a nationwide study of a large-scale patient cohort. Methods Between 2009 and 2011, data were collected by the Korean National Health Insurance Service for 4,658,473 persons aged 40–70 years without thyroid cancer. During the 6-year follow-up period, participants were monitored for the development of thyroid cancer. The relative risks and incidences of thyroid cancer were calculated using multivariate Cox proportional hazards regression analyses after adjusting for age and body mass index. Results At the end of the study, 47,325 subjects (1.0%) were newly diagnosed with thyroid cancer. The risk of thyroid cancer was significantly elevated in men and women with MS or MS components, except for hyperglycaemia (p = 0.723) or hypertriglyceridemia (p = 0.211) in men. The incidence of thyroid cancer per 10,000 person-years in individuals with MS was significantly higher in men (6.2, p < 0.001) and women (21.3, p < 0.001) compared to those without MS. Additionally, the risk of thyroid cancer increased significantly with an increasing number of MS components even in individuals with only one or two MS components. Conclusions MS and its components were significantly associated with increased risk of developing thyroid cancer. Patients with MS or MS components should be regularly screened for thyroid cancer to enable swift therapeutic response in this at-risk population.


Author(s):  
Salome Weiss ◽  
Indrani Sen ◽  
Ying Huang ◽  
Jill M Killian ◽  
W. Scott Harmsen ◽  
...  

Background: Acute aortic syndrome (AAS) includes aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU) and confers high rates of aortic related events. However, the risk of cardiovascular (CV) events in this patient group is unknown. The aim of this study was to define the rates of CV events in an incident cohort of AAS patients. Methods: Medical records and death certificates of all Olmsted County, MN residents with a diagnosis of AAS from 1995-2015 were reviewed and compared to age- and sex- matched population controls. Primary outcome was non-aortic CV mortality. Secondary outcome was overall mortality and first time non-fatal CV event (myocardial infarction (MI), heart failure (HF) or stroke). Events were analyzed using Cox proportional hazards regression adjusting for comorbidities. Results: Of 133 patients with AAS (77 AD, 21 IMH, 35 PAU) 57% were male, median age was 72 (SD 14) and median follow-up was 10 years. Overall survival in AAS cases and controls was 62% versus 83% at 5 years and 44% versus 60% at 10 years (adj HR 1.8, p<.001, 95% CI 1.3-2.4). CV death occurred in 21 (29%) of 73 AAS decedents due to HF (9), MI (5), other cardiac causes (5), stroke (1) and peripheral vascular disease (1). CV-related survival at 5 and 10 years after AAS diagnosis (91% and 81%) was not significantly different from controls (95% and 86%) after adjustment for comorbidities (adj HR 1.8, p=.1, 95% CI 0.9-3.6). AAS was associated with an increased risk of any first time CV event (adj HR 2.6, p<.001, 95% CI 1.6-4.4; Figure), first time diagnosis of MI (adj HR 2.8, p<.001, 95% CI 1.7-4.7) and HF (adj HR 3.2, p<.001, 95% CI 1.6-6.2) but not stroke. When excluding acute events within 14 days of diagnosis, AAS was still associated with a significantly higher mortality (adj HR 1.6, p=.011, 95% CI 1.1-2.4) and an increased risk of any first time CV event (adj HR 2.2, p=.018, 95% CI 1.1-4.1), first time MI (adj HR 2.2, p=.012, 95% CI 1.2-4.1) and HF (adj HR 2.9, p=.006, 95% CI 1.4-6.2) but not stroke. Conclusions: AAS is associated with a higher overall mortality and an increased risk of any first time CV event, first time MI and HF that persists beyond the acute phase. These data highlight the risk of CV events among those with AAS and implicate the need for long-term cardiovascular management in these patients.


2018 ◽  
Vol 48 (6) ◽  
pp. 399-405 ◽  
Author(s):  
Tarra Faulk ◽  
Lauren E. Walker ◽  
Jeffrey T. Howard ◽  
Jud C. Janak ◽  
Jonathan A. Sosnov ◽  
...  

Background: Although rhabdomyolysis has been associated with acute kidney injury and mortality in the short term, the long-term consequences of an episode of rhabdomyolysis remain unknown. We sought to identify the long-term outcomes of rhabdomyolysis, including mortality, renal function, and incidence of hypertension (HTN), among service members initially admitted to the intensive care unit after sustaining a combat injury in Iraq or Afghanistan between February 1, 2002 and February 1, 2011. Methods: Information on age, sex, injury severity score, mechanism of injury, serum creatinine, burn injury, presenting mean arterial pressure, and creatine kinase were retrospectively collected and analyzed for 2,208 patients. Standard descriptive tests were used to compare characteristics of patients with and without rhabdomyolysis. Competing risk Cox proportional hazards models were performed to assess the associated risk of rhabdomyolysis with both HTN and poor renal function. Results: While rhabdomyolysis was associated with HTN on univariate analysis (hazard ratio [HR] 1.30, 95% CI 1.03–1.64; p = 0.029), this difference did not persist on multivariable analysis (HR 1.27, 95% CI 0.99–1.62; p = 0.058). The median estimated glomerular filtration rate (eGFR) was 119 (interquartile range [IQR] 103–128) among those with rhabdomyolysis, compared with 108 (IQR 94–121) in the group without rhabdomyolysis (p < 0.001). Conclusion: After adjustment, patients with rhabdomyolysis were not at an increased risk of HTN compared to patients without rhabdomyolysis. eGFR was paradoxically higher in patients with rhabdomyolysis. There was no association found between rhabdomyolysis and mortality.


2019 ◽  
Vol 37 (03) ◽  
pp. 291-295 ◽  
Author(s):  
Ofer Beharier ◽  
Asnat Walfisch ◽  
Tamar Wainstock ◽  
Irit Szaingurten-Solodkin ◽  
Daniela Landau ◽  
...  

Abstract Objective Animal studies indicate a possible intrauterine immunological imprinting in pregnancies complicated by hypothyroidism. We aimed to evaluate whether exposure to maternal hypothyroidism during pregnancy increases the risk of long-term infectious morbidity of the offspring. Study Design A retrospective cohort study compared the long-term risk of hospitalization associated with infectious morbidity in children exposed and unexposed in utero to maternal hypothyroidism. Outcome measures included infectious diagnoses obtained during any hospitalization of the offspring (up to the age of 18 years). Results The study included 224,950 deliveries. Of them, 1.1% (n = 2,481) were diagnosed with maternal hypothyroidism. Children exposed to maternal hypothyroidism had a significantly higher rate of hospitalizations related to infectious morbidity (13.2 vs. 11.2% for control; odds ratio: 1.2; 95% confidence interval: 1.08–1.36; p = 0.002). Specifically, incidences of ear, nose, and throat; respiratory; and ophthalmic infections were significantly higher among the exposed group. The Kaplan–Meier curve indicated that children exposed to maternal hypothyroidism had higher cumulative rates of long-term infectious morbidity. In the Cox proportional hazards model, maternal hypothyroidism remained independently associated with an increased risk of infectious morbidity in the offspring while adjusting for confounders. Conclusion Maternal hypothyroidism during pregnancy is associated with significant pediatric infectious morbidity of the offspring.


2021 ◽  
pp. 089686082110189
Author(s):  
Mu-Chi Chung ◽  
Tung-Min Yu ◽  
Ming-Ju Wu ◽  
Ya-Wen Chuang ◽  
Chih-Hsin Muo ◽  
...  

Background: The impact of peritoneal dialysis-associated peritonitis (PD peritonitis) on long-term outcomes is uncertain. This nationwide retrospective study was conducted in Taiwan to understand the incidence, risk factors and long-term outcomes of PD peritonitis. Methods: A total of 11,202 incident adult peritoneal dialysis (PD) patients from 2000 to 2010 were collected from a Longitudinal Health Insurance Database and followed up until the end of 2011. Definition of peritonitis, the primary outcome, simultaneously met the diagnosis of peritonitis (International Classification of Diseases, Ninth Revision, Clinical Modification 567) and antibiotic use. Secondary outcomes included the impact of peritonitis on PD discontinuation and survival. Cox proportional hazards models with and without time-dependent variables were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: There were 7634 peritonitis episodes in 4245 patients during the follow-up period. The overall incidence of peritonitis was 0.18 episodes per patient-year. Peritonitis-associated risk factors included older age, female gender, chronic heart failure, cerebrovascular disease, liver cirrhosis and lower monthly income. In an adjusted Cox hazard proportional regression with the time-dependent model, peritonitis patients had a higher risk of PD discontinuation (HR 2.71, 95% CI 2.52–2.92) and mortality (HR 1.68, 95% CI 1.57–1.81) compared to patients without peritonitis. The adjusted HRs for mortality increased with each prior episode: one episode, two episodes and more than two episodes (all p < 0.05). The adjusted HRs for PD discontinuation also increased with the frequency of peritonitis. These negative effects were greatest during the first year and persisted significantly after 5 years. In a sensitivity analysis in which peritonitis within 30 days of death or PD discontinuation was excluded, peritonitis patients still had significantly increased risk of PD discontinuation and mortality compared to patients without peritonitis. Conclusions: Although peritonitis incidence was low, our findings reveal that peritonitis carried acute and long-term sequelae of higher PD discontinuation and lower patient survival.


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