Perioperative outcomes and long-term quality of life after total pancreatectomy.

BACKGROUND: Total pancreatectomy is required to treat diseases involving the entire pancreas, and is characterized by high morbidity rates and impaired long-term quality of life (QoL). To date, risk factors associated with perioperative and long-term outcomes have not been determined fully. METHODS: Data from patients undergoing total pancreatectomy between 2000 and 2014 at two high-volume centres were analysed retrospectively to assess risk factors for major surgical complications. Short Form (SF) 36, European Organisation for Research and Treatment of Cancer QLQ-PAN26 and Audit of Diabetes Dependent questionnaires, as well as an original survey were used to investigate factors influencing QoL. RESULTS: A total of 329 consecutive patients underwent total pancreatectomy in the two centres. Overall, total pancreatectomy was associated with a morbidity rate of 59·3 per cent and a 30-day mortality rate of 2·1 per cent. Age over 65 years and long duration of surgery (more than 420 min) were independently associated with major complications (at least Clavien-Dindo grade III). QoL analysis was available for 94 patients (28·6 per cent) with a median follow-up of 63 (i.q.r. 20-109) months; the most common indication for total pancreatectomy in these patients was intraductal papillary mucinous neoplasms (46 per cent). Both physical (PCS) and mental (MCS) component summary scores of SF-36® were lower after total pancreatectomy compared with scores for a normative population (P = 0·020 and P < 0·001 respectively). Linear regression analysis showed that young age, abdominal pain and worse perception of body image were negatively associated with the PCS, whereas diabetes, sexual satisfaction and perception of body image affected MCS. CONCLUSION: Total pancreatectomy can be performed with acceptable morbidity and mortality rates. Older patients had a higher risk of postoperative complications but reported better QoL than younger patients.

ANTECEDENTES: La pancreatectomía total es una cirugía necesaria para tratar enfermedades que afectan a la totalidad el páncreas y se caracteriza por una alta morbilidad y una disminución de la calidad de vida (QoL) a largo plazo. Hasta la fecha, los factores de riesgo asociados a los resultados perioperatorios y a largo plazo no han sido completamente determinados. MÉTODOS: Los datos de los pacientes que se sometieron a una pancreatectomía total desde el año 2000 al 2015 en dos centros de alto volumen se analizaron retrospectivamente para evaluar los factores de riesgo de las complicaciones quirúrgicas mayores. Se utilizaron el SF-36, el EORTC-PAN-26, los cuestionarios ADD-QoL y una encuesta original para investigar los factores que afectan la QoL. RESULTADOS: Un total de 329 pacientes consecutivos se sometieron a una pancreatectomía total en los dos centros. En general, la pancreatectomía total se asoció a un 59,3% de morbilidad y un 2,1% de mortalidad a los 30 días. La edad > 65 años y el tiempo operatorio prolongado (> 420 minutos) se asociaron de forma independiente a las complicaciones Clavien-Dindo ≥ III. El análisis de QoL estuvo disponible en 94 (28,6%) de los pacientes con una mediana de seguimiento de 63 meses (rango intercuartílico 20-109) y la indicación más común fue una neoplasia papilar mucinosa intraductal (IPMN) (45,7%). Las puntuaciones del SF-36 fueron más bajas en ambos componentes sumatorios físico (PCS) y mental (MCS) (P = 0,002; P < 0,001) en comparación con una población normal. El modelo de regresión lineal mostró que la edad joven, el dolor abdominal y la peor percepción de la imagen corporal se asociaron negativamente con el PCS; mientras que la diabetes, la satisfacción sexual y la percepción de la imagen corporal afectaron al MCS. CONCLUSIÓN: Se puede realizar una pancreatectomía total con morbilidad y mortalidad aceptables. Los pacientes de mayor edad tienen un riesgo más elevado de complicaciones postoperatorias, pero presentaron mejor QoL que los pacientes más jóvenes.

Bone density changes following surgical correction of femoroacetabular impingement deformities.

OBJECTIVE: Femoroacetabular impingement (FAI) involves abnormal hip biomechanics due to deformities and is associated with osteoarthritis. Bone mineral density (BMD) in the acetabulum is higher in subjects with convex femoral (cam) FAI deformities compared to control subjects. The objective of this study was to assess post-operative changes of BMD with and without surgical correction of the cam deformity. DESIGN: Thirteen patients with bilateral cam deformities but unilateral symptoms underwent pre-operative and follow-up computed tomography (CT) scans of both hips. The deformity was surgically removed from the symptomatic hip. BMD was measured in regions of interest (ROI) around the superior acetabulum from CT scans at both time points. The contralateral untreated hip was used as a within-patient control. Changes in BMD were assessed by two-way repeated measures ANOVA (side, time) and paired t-tests. RESULTS: A greater BMD decrease was seen in the treated compared to the untreated hip (P < 0.0018). BMD within the superior acetabulum decreased by 39 mg/cc on the treated side (P < 0.0001) but only 9 mg/cc (P = 0.15) in the untreated contralateral hip. These changes represent 7.1% and 1.7% of the pre-operative BMD on the respective sides. CONCLUSIONS: BMD decreased in the treated hip, suggesting a positive effect of surgical correction in relieving stresses within the hip joint. Longer term follow-up is required to assess the ultimate fate of the articular cartilage within the joint. This study showed that surgical correction of the cam deformity in patients with FAI may alter the pathological biomechanics within the joint.

Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases.

BACKGROUND: This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. METHODS: A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0-1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. CONCLUSION: The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.

The current state of surgery for pancreatic cancer.

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the United States, with a dismal 5-year survival of only 6% for all stages. Surgical resection offers the best opportunity for prolonged survival at this time, but is limited to patients with locally resectable tumors and no distant metastases. Although only 10-20% of patients present with early stage disease are amenable to surgical resection, remarkable advancements have been made over the past several decades leading to improved morbidity and mortality after pancreatic resection. This article will review the current state of pancreatic surgery including its role in the multidisciplinary approach to pancreatic cancer treatment, advances and controversies in surgical technique, and the limitations of surgical therapy that will need to be addressed in the future to improve survival for patients with pancreatic cancer.

p47phox and reactive oxygen species production modulate expression of microRNA-451 in macrophages.

The production of microRNAs (miRNA) is influenced by various stimuli, including environmental stresses. We hypothesized that reactive oxygen species (ROS)-associated stress could regulate macrophage miRNA synthesis. miRNAs undergo unique steps of maturation processing through either one of two pathways of cytoplasmic processing. Unlike the canonical pathway, the regulation of alternative cytoplasmic processing of miRNA has not been fully elucidated yet. We cultured bone marrow derived macrophages (BMDM) from wild type (WT) and p47(phox-/-) mice and profiled miRNA expression using microarrays. We analyzed 375 miRNAs including four endogenous controls to normalize the data. At resting state, p47(phox-/-) BMDM has the markedly reduced expression of miR-451 compared to WT BMDM, without other significant differences. Unlike majority of miRNAs, miR-451 goes through the unique alternative processing pathway, in which Ago2 plays a key role. In spite of significant reduction of mature miR-451, however, its precursor form, pre-mir-451, was similar in both BMDMs, suggesting that the processing of pre-mir-451 is impaired in p47(phox-/-) BMDM. Moreover, p47(phox-/-) BMDM expressed significantly reduced level of Ago2. In contrast, Ago2 mRNA levels were similar in WT and p47(phox-/-) BMDM, suggesting a post-transcriptional defect of Ago2 production in p47(phox-/-) macrophages, which resulted in impaired processing of pre-miR-451. In order to examine the functional significance of miR-451 in macrophages, we cultured BMDMs from miR-451 knock-out mice. Of interest, miR-451-deficient BMDM exhibited reduced ROS generation upon zymosan stimulation, compared to WT BMDM. Our studies suggest functional crosstalk between ROS and miR-451 in the regulation of macrophage oxidant stress.

Laparoscopic pancreatic surgery.

Laparoscopic pancreatectomy may be associated with lower operative morbidity, less postoperative pain, lower wound infection rates, decreased physiological stress, and fewer postoperative hernias and bowel obstructions. In this review, we summarize the current data on laparoscopic and robotic assisted pancreaticoduodenectomy/distal pancreatectomy/central pancreatectomy. We reviewed the indications, the perioperative and oncologic outcomes, and the cost analysis following minimally invasive pancreatic resections. In conclusion, we found minimally invasive approaches to pancreatic resections are feasible, safe, and appear to have comparable oncologic outcomes to the standard open approaches when performed by experienced surgeons at high-volume centers. The potential advantages of a minimally invasive approach to pancreatic surgery, such as reduced blood loss and shorter length of hospital stay, have now been well established. The overall cost of laparoscopic pancreatectomy appears to be similar to that of the open approach.

Early atherogenesis and visceral fat in obese adolescents.

BACKGROUND/OBJECTIVES: Little information is available as to the cause of increased thickening of the intima-media of the carotid artery (cIMT) in the pediatric population. Therefore, cIMT was compared in obese adolescents and normal-weight controls, and associations between cIMT and lipid and non-lipid cardiovascular risk factors were assessed. SUBJECTS/METHODS: Subjects included 61 obese non-diabetic male and female volunteers aged 12-18 years inclusive with a body mass index (BMI) >95th percentile for age and 2-h blood glucose <200 mg dl(-1) matched to 25 normal-weight control volunteers with normal glucose levels. Each subject underwent a 2-h glucose tolerance test and measurement of hemoglobin A1c, ultrasensitive C-reactive protein, fasting insulin, blood lipids, visceral, subcutaneous abdominal and hepatic fat, and cIMT. RESULTS: Maximum cIMT was 0.647±0.075 mm in the obese subjects versus 0.579±0.027 mm in normal-weight controls (P<0.001). There was no difference in maximum cIMT between male and female subjects. There were significant correlations between maximum cIMT and BMI z-score, 2-h glucose, fasting insulin, homeostasis model assessment (HOMA), total low-density lipoprotein (LDL) cholesterol, very LDL cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, triglycerides, remnant lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, lipoprotein(a), apoprotein B100, abdominal subcutaneous fat volume, visceral fat volume and hepatic phase difference. On multiple regression analysis, visceral fat was the most significant predictor of maximum cIMT. Two-hour blood glucose, HOMA and systolic blood pressure were also significant predictors of maximum cIMT. CONCLUSIONS: cIMT was increased in the obese adolescents compared with the normal-weight-matched controls. Visceral fat was a key predictor of arterial wall thickening in these subjects. The results suggest that the focus of cardiovascular disease prevention in the adolescent obese should be visceral obesity, and not blood lipids or lipid subclasses.

The indirect alloresponse impairs the induction but not maintenance of tolerance to MHC class I-disparate allografts.

We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance.

Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts in miniature Swine.

UNLABELLED: We have previously reported that tolerance to class I disparate lung allografts in miniature swine could be induced using an intensive 12-day course of tacrolimus and that pretransplant sensitization with immunogenic MHC class I allopeptides failed to block the induction of tolerance. We also have previously reported the importance of the presence of the thymus in the induction of tolerance to isolated heart, kidney, and combined heart-kidney transplants. In this study, we examined the impact of thymectomy on tolerance induction in lung transplantation. METHODS: Orthotopic left lung transplantation was performed using MHC class I-disparate donors. The recipients received a 12-day course of high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the swine 21 days prior to transplantation. Lung grafts were monitored by chest radiography and serial open lung biopsy. RESULTS: All euthymic recipients maintained their grafts for over 1 year. None of the thymectomized recipients has experienced graft loss in the 6 to 10 months following transplantation. Although isolated lesions of obliterative bronchiolitis were occasionally seen in one thymectomized animal on biopsy, donor-specific unresponsiveness has been observed on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co-culture assays have shown that recipient lymphocytes can strongly inhibit the normally robust response of naïve recipient-matched lymphocytes to donor antigen. This inhibition was not seen when using stimulators primed with third-party antigens against appropriate targets. CONCLUSIONS: These data suggest that thymus-independent peripheral regulatory mechanisms may be sufficient to induce and maintain long-term acceptance of the lung allografts.

The role of indirect recognition of MHC class I and II allopeptides in a fully mismatched miniature swine model of lung transplantation.

UNLABELLED: Considerable evidence suggests that indirect recognition of MHC allopeptides plays an important role in solid-organ rejection. Here, we examine whether immunization with class I or class II allopeptides accelerates rejection in a fully MHC-mismatched lung transplant model in miniature swine. METHODS: Recipients were immunized with either donor-derived class I or class II peptides. Sensitization to the peptides was confirmed by DTH testing and in vitro proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully mismatched lungs using only a 12-day course of tacrolimus. RESULTS: One control animal rejected its graft on postoperative day 103, while the others maintained their grafts for over 1 year. In the class I peptide-immunized group, two recipients rejected their grafts (days 14 and 52). The third animal has not rejected the graft (day 120, experiment is ongoing). In contrast, in the class II-peptide immunized group, only one animal rejected its graft on day 52, while the others maintained their grafts over 1 year. Both anti-donor IgM and IgG antibodies were detectable in all acute rejectors, although no alloantibody was detectable in long-term acceptors. Regardless of the fate of the graft, all animals have maintained their proliferative responses to the peptides. However, only acceptors maintained donor-specific hyporesponsiveness in cell-mediated lymphocytotoxity and mixed lymphocyte reaction assays. CONCLUSIONS: Pretransplant sensitization of lung allograft recipients to donor allopeptides accelerates graft rejection. This appears particularly true for class I-derived allopeptides, suggesting that class II molecules may be less antigenic when presented indirectly.

Teaching social skills to people with autism.

The treatment of social skills deficits remains one of the most challenging areas in meeting the needs of people with autism. Difficulties in understanding social stimuli, in initiating and responding to social bids, and in appreciating the affect that is intrinsic to social interactions can be baffling for people with autism. Researchers and practitioners of applied behavior analysis have tried a variety of strategies for teaching social skills. This article examines a range of useful procedures for teaching social skills to people with autism, including skills that are adult mediated, peer mediated, and child-with-autism mediated. The authors also consider the potential of classwide interventions in inclusive settings, pivotal response training, and the use of scripts to teach social initiations.

Trapping-mediated dissociative chemisorption of cycloalkanes on Ru(001) and Ir(111): influence of ring strain and molecular geometry on the activation of C-C and C-H bonds.

We have measured the initial probabilities of dissociative chemisorption of perhydrido and perdeutero cycloalkane isotopomers on the hexagonally close-packed Ru(001) and Ir(111) single-crystalline surfaces for surface temperatures between 250 and 1100 K. Kinetic parameters (activation barrier and preexponential factor) describing the initial, rate-limiting C-H or C-C bond cleavage reactions were quantified for each cycloalkane isotopomer on each surface. Determination of the dominant initial reaction mechanism as either initial C-C or C-H bond cleavage was judged by the presence or absence of a kinetic isotope effect between the activation barriers for each cycloalkane isotopomer pair, and also by comparison with other relevant alkane activation barriers. On the Ir(111) surface, the dissociative chemisorption of cyclobutane, cyclopentane, and cyclohexane occurs via two different reaction pathways: initial C-C bond cleavage dominates on Ir(111) at high temperature (T > approximately 600 K), while at low temperature (T < approximately 400 K), initial C-H bond cleavage dominates. On the Ru(001) surface, dissociative chemisorption of cyclopentane occurs via initial C-C bond cleavage over the entire temperature range studied, whereas dissociative chemisorption of both cyclohexane and cyclooctane occurs via initial C-H bond cleavage. Comparison of the cycloalkane C-C bond activation barriers measured here with those reported previously in the literature qualitatively suggests that the difference in ring-strain energies between the initial state and the transition state for ring-opening C-C bond cleavage effectively lowers or raises the activation barrier for dissociative chemisorption via C-C bond cleavage, depending on whether the transition state is less or more strained than the initial state. Moreover, steric arguments and metal-carbon bond strength arguments have been evoked to explain the observed trend of decreasing C-H bond activation barrier with decreasing cycloalkane ring size.

Identification of a 1-megabase consensus region of deletion at 1p36.3 in primary neuroblastomas.

BACKGROUND: Deletion of the distal short arm of chromosome 1 occurs frequently in neuroblastoma. In addition, neuroblastoma has been described in children with constitutional deletions within 1p36, supporting the existence of one or more neuroblastoma suppressor genes within this region. PROCEDURE: We have pursued a 1p36 tumor suppressor gene identification strategy that has included deletion mapping of 566 primary neuroblastomas and 46 neuroblastoma-derived cell lines, and have determined the parental origin of the deleted 1p homologue in 44 cases to determine whether there is evidence for genomic imprinting within this region. RESULTS AND CONCLUSIONS: We have identified a 1-Mb consensus region of deletion within 1p36.3 defined by primary tumor deletions, constructed a physical map of the region that is being sequenced to completion, and have identified and prioritized candidate genes within this region for further analyses.

Localization of a hereditary neuroblastoma predisposition gene to 16p12-p13.

BACKGROUND: Hereditary predisposition to develop neuroblastoma segregates as an autosomal dominant Mendelian trait. PROCEDURE: We have performed linkage analysis on 10 families with neuroblastoma to localize a hereditary neuroblastoma predisposition gene (HNB1). RESULTS: A single genomic interval at chromosome bands 16p12-p13 was consistent with linkage (lod = 3.46), and identification of informative recombinants defined a 25.9-cM critical region between D16S748 and D16S3068. Loss of heterozygosity was identified in 5/12 familial (42%) and 55/259 nonfamilial (21%) neuroblastomas at multiple 16p polymorphic loci. A 12.8-cM smallest region of overlap of deletions was identified within the interval defined by linkage analysis (tel-D16S764-D16S412-cen). CONCLUSIONS: Taken together, these data suggest that HNB1 is located at 16p12-p13 and that inactivation of this gene may contribute to the pathogenesis of nonfamilial neuroblastomas.

ABC-me: a novel mitochondrial transporter induced by GATA-1 during erythroid differentiation.

Transcription factor GATA-1 is essential for normal erythropoiesis. GATA-binding sites are consistently found in promoters or enhancers of genes expressed selectively in erythroid cells. To discover novel GATA-1-regulated genes, we searched for GATA-1-activated transcripts in G1E cells, an erythroid line derived from GATA-1(-) embryonic stem cells. By subtractive analysis, we identified a new ATP-binding cassette (ABC) transporter that is strongly and rapidly induced by GATA-1. This protein, named ABC-me (for ABC-mitochondrial erythroid), localizes to the mitochondrial inner membrane and is expressed at particularly high levels in erythroid tissues of embryos and adults. ABC-me is induced during erythroid maturation in cell lines and primary hematopoietic cells, and its overexpression enhances hemoglobin synthesis in erythroleukemia cells. The ABC proteins participate in diverse physiological processes by coupling ATP hydrolysis to the transport of a variety of substrates across cell membranes. We speculate that ABC-me, a newly identified erythroid-expressed ABC superfamily member, may mediate critical mitochondrial transport functions related to heme biosynthesis.

Reversal of caffeine withdrawal by ingestion of a soft beverage.

Followlng regular use, acute cessation of caffeine is associated with a characteristic withdrawal syndrome. Despite this, caffeine remains popular with its consumers. The aim of this study was to examine the physiologic and psychologic effects of small caffeine doses, administered in the form of a market-leading soft drink, on healthy women who were acutely withdrawn from caffeine. After 48-h abstinence and overnight fast, 11 healthy (22 to 40 years) female volunteers, all regular caffeine users (daily consumption 143 to 773 mg) consumed using a double-blind. randomized, controlled cross-over design either 2 tins of regular or caffeine-free Diet Coke. On both visits a Mars bar was eaten to prevent hypoglycaemia. Thus, the caffeine load was 76 or 10 mg respectively. Following ingestion of regular Diet Coke, there was a l0% fall in middle cerebral artery velocity (95% CI [6%-l4%], p < 0.005 versus caffeine free) and improvement in feelings of pleasure (p < 0.046) and energy (p < 0.037). Intellectual function (4-choice reaction time) was unaffected by caffeine status. On both visits, ingestion of Diet Coke induced a pressor response (maximum rise in systolic pressure +15+/- 2 mm Hg with caffeine and +l2 +/- 2 mm Hg with caffeine-free beverage, both p < 0.001 compared with baseline). In conclusion, in women acutely withdrawn from caffeine, ingestion of a popular soft beverage containing modest amounts of caffeine is associated with demonstrable physiologic and psychologic effects.

Loss of heterozygosity at 1p36 independently predicts for disease progression but not decreased overall survival probability in neuroblastoma patients: a Children's Cancer Group study.

PURPOSE: To determine the independent prognostic significance of 1p36 loss of heterozygosity (LOH) in a representative group of neuroblastoma patients. PATIENTS AND METHODS: Diagnostic tumor specimens from 238 patients registered onto the most recent Children's Cancer Group phase III clinical trials were assayed for LOH with 13 microsatellite polymorphic markers spanning chromosome band 1p36. Allelic status at 1p36 was correlated with other prognostic variables and disease outcome. RESULTS: LOH at 1p36 was detected in 83 (35%) of 238 neuroblastomas. There was a correlation of 1p36 LOH with age at diagnosis greater than 1 year (P = .026), metastatic disease (P<.001), elevated serum ferritin level (P<.001), unfavorable histopathology (P<.001), and MYCN oncogene amplification (P<.001). LOH at 1p36 was associated with decreased event-free survival (EFS) and overall survival (OS) probabilities (P<.0001). For the 180 cases with single-copy MYCN, 1p36 LOH status was highly correlated with decreased EFS (P = .0002) but not OS (P = .1212). Entering 1p36 LOH into a multivariate regression model suggested a trend toward an independent association with decreased EFS (P = .0558) but not with decreased OS (P = .3687). Furthermore, allelic status at 1p36 was the only prognostic variable that was significantly associated with decreased EFS in low-risk neuroblastoma patients (P = .0148). CONCLUSION: LOH at 1p36 is independently associated with decreased EFS, but not OS, in neuroblastoma patients. Determination of 1p36 allelic status may be useful for predicting which neuroblastoma patients with otherwise favorable clinical and biologic features are more likely to have disease progression.