Eduardo A. Perez

Pediatric Thyroid Carcinoma: Incidence and Outcomes in 1753 Patients

OBJECTIVE To examine outcomes and predictors of survival for pediatric patients with thyroid carcinoma. METHODS The Surveillance, Epidemiology, and End Results (SEER) registry from 1973 to 2004 was queried for all patients with thyroid carcinoma less than 20 y of age. RESULTS A total of 1753 patients with malignant thyroid neoplasms were identified with an age-adjusted annual incidence of 0.54 cases per 100,000 persons. There has been a significant increase in the annual incidence by 1.1% per y. Female patients outnumbered males 4 to 1. Tumors were classified as papillary (n=1044, 60%), follicular variant of papillary (n=389, 23%), follicular (n=165, 10%), and medullary (n=87, 5%). The majority of patients presented with localized and regional disease. Overall mean survival time (MST) was 30.5 y. The MST for females was 40 y, whereas males survived an average of 20.4 y (P=0.0001). Patients with medullary cancer had significantly shorter mean survival than those with papillary cancer (P=0.006). Surgical treatment significantly improved outcome. Multivariate analysis demonstrated that male gender, nonpapillary histology, distant disease, and no surgery were all independent prognostic factors of worse outcome. For patients with medullary thyroid carcinoma, radiation therapy was also identified as an independent predictor of lower survival. CONCLUSION The incidence of pediatric thyroid cancer is increasing. Females have a higher incidence than males, but enjoy longer survival. Papillary thyroid cancer has overall excellent survival. Male gender, nonpapillary tumor, distant metastases, and nonsurgical treatment all predict worse outcome.

Should soft tissue sarcomas be treated at high-volume centers? An analysis of 4205 patients

Objective:To define the prognostic significance of surgical center case volume on outcome for soft tissue sarcoma (STS). Methods:STS cases registered in the Florida Cancer Data System (FCDS) between 1981 and 2001 were analyzed. Medical facilities were ranked by STS operative volume. Facilities above the 67th percentile for volume were defined as high-volume centers (HVCs). Results:Of the 4205 operative cases of STS identified, 68.1% were treated at low-volume centers (LVCs) and 31.9% at HVCs. A larger proportion of high-grade tumors (53.8% vs. 44.3%) and lesions over 10 cm (40.7% vs. 28.7%) were resected at HVC (P < 0.001). The 30-day mortality was 0.7% for HVC and 1.5% for LVC (P = 0.028), and mortality rates at 90 days were 1.6% and 3.6%, respectively (P = 0.001). Median survival was 40 months at HVC and 37 months at LVC (P = 0.002). Univariate analysis demonstrated significantly improved survival at HVC for high-grade tumors (median 30 months vs. 24 months, P = 0.001), lesions over 10 cm (28 months vs. 19 months, P = 0.001) and truncal or retroperitoneal sarcomas (39 months vs. 31 months, P = 0.011). Limb amputation rate was lower (9.4% vs. 13.8%, P = 0.048) and radiation and chemotherapy were more frequently administered at HVC (OR = 1.54). On multivariate analysis, treatment at a HVC was a significant independent predictor of improved survival (OR = 1.292, P = 0.047). Conclusions:STS patients treated at HVC have significantly better survival and functional outcomes. Patients with either large (>10 cm), high-grade or truncal/retroperitoneal tumors should be treated exclusively at a high-volume center.

Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair

Interleukin‐6 (IL‐6) is an important mediator of liver regeneration and repair that is also elevated in chronic liver diseases, including fatty liver of obesity and cirrhosis. IL‐6 has been reported both to delay and accelerate liver regeneration. We examined the effects on liver injury and regeneration of a continuous administration of exogenous IL‐6 to mice by injection of an IL‐6–expressing CHO‐cell line in athymic nude mice and by osmotic mini‐pump delivery of recombinant murine IL‐6. Short‐term IL‐6 administration (1‐2 days) accelerated early recovery of liver mass, whereas more long‐term administration (5‐7 days) markedly impaired liver regeneration. Similarly, short‐term IL‐6 treatment increased hepatic resistance to the lethal effects of the Fas agonist Jo‐2, but on more prolonged IL‐6 exposure the Jo‐2 resistance vanished. IL‐6 administration initially induced expression of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL, correlating with protection against Fas‐mediated cell death. More prolonged IL‐6 administration, however, resulted in marked induction of the pro‐apoptotic protein Bax. This result coincided with increased activation of the type II or intrinsic, mitochondrial path to cell death, manifested by increased caspase‐9 activation and increased cytochrome c release after Jo‐2 exposure. These data demonstrate that IL‐6 can function acutely to improve hepatic regeneration and repair, but that more chronic exposure not only abolishes the protective effects of IL‐6, but actually sensitizes the liver to injury and death. In conclusion, elevated IL‐6 in certain chronic liver diseases contributes to an increased likelihood of liver failure after injury. (HEPATOLOGY 2006;43:474–484.)

African American and Poor Patients Have a Dramatically Worse Prognosis for Head and Neck Cancer : An Examination of 20,915 Patients

Differences in cancer survival based on race, ethnicity, and socioeconomic status (SES) are a major issue. To identify points of intervention and improve survival, the authors sought to determine the impact of race, ethnicity, and socioeconomic status for patients with cancers of the head and neck (HN).

Malignant pancreatic tumors: incidence and outcome in 58 pediatric patients.

OBJECTIVE The purpose of the study was to examine current incidence trends and outcomes for children with pancreatic malignancies. METHODS The Surveillance, Epidemiology, and End Results registry (1973-2004) was examined for pediatric patients with pancreatic malignancies (up to 19 years of age). RESULTS Malignant pancreatic neoplasms were identified in 58 patients. Females outnumbered males 1.9 to 1 (38 vs 20) for an age population-adjusted incidence of 0.021 and 0.015 per 100,000. Overall, 70% (n = 41) of patients were white. Asians had the highest incidence. Tumors were classified as exocrine (n = 31, 53.4%), endocrine (n = 19, 32.8%), or sarcomas (n = 5, 8.6%). Exocrine tumors included pancreatoblastoma (n = 10), solid-cystic tumor (SCT) (n = 10), ductal adenocarcinoma (DA) (n = 7), and acinar cell carcinoma (ACC) (n = 4). All SCTs and 80% of pancreatoblastomas were seen in females, whereas males had a higher incidence of DA 71% (P = .036). Ductal adenocarcinoma, SCT, acinar cell carcinoma, sarcomas, and endocrine tumors were more common in children older than 10 years, whereas pancreatoblastoma was more common in younger children (P = .045). Almost half of patients (n = 25) presented with distant metastasis; of these, 44% were endocrine tumors. Survival was significantly greater for female patients (P = .004) and for those who had surgery (P = .001) by both univariate and multivariate analysis. There was a significant difference in tumor type 15-year survival with DA having the worst (23%) and SCT the best (100%). CONCLUSIONS Pediatric pancreatic neoplasms are uncommon and carry a variable prognosis. Both female sex and surgery were independent predictors of improved survival.

Incidence and Outcomes of Malignant Pediatric Lung Neoplasms

BACKGROUND We sought to define current incidence trends and outcomes for children with lung and bronchus tumors. METHODS The SEER registry was queried from 1973 to 2004 for all patients with pulmonary tumors less than 20 y of age. RESULTS Overall, 160 patients were identified. The age-adjusted incidence has remained stable at 0.049 per 100,000 persons. The median age at diagnosis was 16 y. Whites had the highest age-adjusted population incidence at 0.056 per 100,000. Most tumors arose in the lower lobe (37%), followed by the upper lobe (31.2%). The most common histology was endocrine tumor (51.6%), followed by sarcoma (11%), and mucoepidermoid tumor (9%). Overall survival was greater than 381 mo with a 15-y survival of 65%. Males had better survival (>381 versus 288 months). Endocrine and mucoepidermoid tumors had the best survival. Small cell carcinoma had the worst median survival at less than 5 mo. Squamous cell carcinoma and adenocarcinoma both had a 14-mo median survival. Median survival for nonsurgically treated patients was 14 mo with a 10-y survival rate of 32%. Surgery improved the 10-y survival to 75% (P<0.0001). Multivariate analysis demonstrated nonsurgical treatment and nonendocrine tumor histology to be independent prognostic factors of death. CONCLUSION The incidence of pediatric lung cancer remains stable. Several factors, including nonsurgical treatment and nonendocrine tumors confer a poor prognosis. Early diagnosis and surgical therapy provide the best chance for survival.

A review of 218 pediatric cases of hepatocellular carcinoma

PURPOSE This study evaluates the incidence trends and clinical outcomes of children with hepatocellular carcinoma (HCC) and assesses factors predictive of patient survival. METHODS The Surveillance, Epidemiology, and End Results registry was queried from 1973 to 2009 for all patients between ages 0 and 19 with primary HCC. Demographics, tumor histology, surgical intervention, and patient survival were collected. RESULTS Overall, 218 patients were identified. The annual age-adjusted incidence was 0.05 cases per 100,000 in 2009. Fibrolamellar subtype tumors were exclusive to children >5years old and exhibited greater survival compared to non-fibrolamellar subtype (57% vs. 28%, respectively, p=0.002). Tumor extirpation for patients with resectable disease significantly improved overall survival at 5years compared to no surgery (60% vs. 0%, respectively, p<0.0001). Overall 5-, 10- and 20-year survival for the entire cohort was 24%, 23%, and 8%, respectively. Independent prognostic factors of lower mortality according to multivariate analysis were surgical resection (hazard ratio (HR)=0.18), non-Hispanic ethnicity (HR=0.52), and local disease at presentation (HR=0.46). CONCLUSION Over the past four decades, the incidence of HCC has remained relatively stable. Children of Hispanic ethnicity have high mortality rates. However, HCC resection for curative intent significantly improves outcomes.

Are many community hospitals undertreating breast cancer?: lessons from 24,834 patients.

Objective:To compare treatment patterns and long-term outcomes between teaching and community hospitals treating patients with infiltrating ductal carcinoma (IDC). Methods:All IDCs from the Florida Cancer Data System from 1994 to 2000 were examined. Results:Overall, 24,834 operative cases of IDC were identified. Teaching hospitals treated 11.3% of patients with a larger proportion of stage III and IV disease (39.8% vs. 33.0%). Five- and 10-year overall survival rates at teaching hospitals were 84% and 72%, compared with 81% and 69% at high-volume community hospitals and 77% and 63% at low-volume hospitals (P < 0.001). The greatest differences on survival were observed in patients with advanced IDC. Examination of practice patterns demonstrated that multimodality therapy was most frequently administered in teaching hospitals. Breast-conserving surgery was more frequently performed at teaching hospitals (41.5% vs. 38.9% P = 0.008). On multivariate analysis, it was found that treatment at a teaching hospital was a significant independent predictor of improved survival (hazard ratio = 0.763, P < 0.001). This survival benefit was greater and independent of high-volume center status (hazard ratio = 0.903, P < 0.02). Conclusions:Patients with IDC treated at teaching hospitals have significantly better survival than those treated at high-volume centers or community hospitals, particularly in the setting of advanced disease. Poorer long-term outcomes for IDC at community hospitals seem to be, at least in part, because of decreased use of proven life-extending adjuvant therapies. These results should encourage community hospitals to institute changes in treatment approaches to invasive breast cancer to optimize patient outcomes.

Value of computed tomographic angiography in neck and extremity pediatric vascular trauma

PURPOSE We sought to define the sensitivity and specificity of computed tomographic angiography (CTA) in pediatric vascular injuries. METHODS All neck and extremity CTAs performed in pediatric patients at a level 1 trauma center were reviewed from 2001 to 2007. RESULTS Overall, 78 patients were identified with an average age of 15.0 +/- 4.0 (0-18 years). Males outnumbered females 3.6:1. CTA was performed for 41 penetrating and 37 blunt traumas. Most penetrating injuries were due to missile wounds (71%) or stab wounds (17%). Eleven major vascular injuries resulted from penetrating trauma. For penetrating trauma, CTA was 100% sensitive and 93% specific. CTA for penetrating trauma had a positive predictive value (PPV) of 85% and negative predictive value (NPV) of 100%. Most blunt injuries were due to motor vehicle accidents (57%), followed by pedestrian hit by car (27%). Eight major vascular injuries resulted from blunt trauma. For blunt trauma, CTA was 88% sensitive and 100% specific. CTA for blunt trauma had a PPV of 100% and an NPV of 97%. The accuracy for penetrating and blunt trauma was 95% and 97%, respectively. CONCLUSIONS CTA is highly sensitive, specific, and accurate for pediatric neck and extremity vascular trauma.

Predictors of survival and incidence of hepatoblastoma in the paediatric population

OBJECTIVES This study evaluates current trends in incidence, clinical outcomes and factors predictive of survival in children with hepatoblastoma (HB). METHODS The Surveillance, Epidemiology and End Results (SEER) database was queried for the period 1973-2009 for all patients aged <20 years with HB. RESULTS A total of 606 patients were identified. The age-adjusted incidence was 0.13 patients per 100 000 in 2009. An annual percentage change of 2.18% (95% confidence interval (CI) 1.10-3.27; P < 0.05) was seen over the study period. Overall survival rates at 5, 10 and 20 years were 63%, 61% and 59%, respectively. Ten-year survival rates significantly improved in patients with resectable disease who underwent operative treatment in comparison with those with non-resectable HB (86% versus 39%; P < 0.0001). Multivariate analysis showed surgical treatment (hazard ratio (HR) = 0.23, 95% CI 0.17-0.31; P < 0.0001), Hispanic ethnicity (HR = 0.61, 95% CI 0.43-0.89; P = 0.01), local disease at presentation (HR = 0.43, 95% CI 0.29-0.63; P < 0.0001) and age < 5 years (HR = 0.63, 95% CI 0.41-0.95; P < 0.03) to be independent prognostic factors of survival. CONCLUSIONS The incidence of paediatric HB has increased over time. Hepatoblastoma is almost exclusively seen in children aged < 5 years. When HB presents after the age of 5 years, the prognosis is most unfavourable. Tumour extirpation markedly improves survival in paediatric patients with local disease.