The introduction of Kasai portoenterostomy has dramatically improved the management and survival of children with biliary atresia. The success rate of this operation worldwide varies with different ...centers. In this respect, many authors have studied the correlation of a successful outcome with various factors, such as the experience and workload of the surgical center, the use of postoperative steroids, the underlying biliary anatomy, as well as the age of patients at the time of the operation. Indeed, the age of 60 days has been used by clinicians as a critical time beyond which the rate of success of the Kasai operation markedly reduces. Despite this worldwide adoption, clear evidence supporting this critical operative time is still lacking. We undertook a review of our experience in the management of children with biliary atresia and focused specifically on the issue of the timing of operation. We showed that performing the Kasai operation beyond the age of 60 days was not associated with a worse outcome and that a high percentage of patients could still achieve good bile flow with normal bilirubin postoperatively. Thus, we believe that until the age of 100 days, the age of the patients does not play a significant role in determining the success of the Kasai operation.
•We externally validated 22 dose-volume constraints of the thyroid gland using long-term endocrine outcomes of 488 HNC patients.•Over a median follow-up period of 6.8 years, 42.0 % of patients ...developed post-radiation primary hypothyroidism.•Thyroid VS60 had the largest area under time-dependent ROC curve of 0.698 at 5 years after radiotherapy.•Thyroid VS60 at a cutoff value of 10 cc had the highest F-score of 0.53.•The 5-year hypothyroidism risks of patients with thyroid VS60 ≥ 10 cc and < 10 cc were 14.7 % and 38.2 %, respectively.
Post-radiation primary hypothyroidism is a common late complication in head and neck cancer (HNC) survivors. No radiation dose-volume constraint of the thyroid gland has been externally validated for predicting long-term thyroid function outcomes.
This external validation study evaluated the diagnostic properties of 22 radiation dose–volume constraints of the thyroid gland proposed in the literature. Radiation dosimetric data from 488 HNC patients who underwent neck irradiation from January 2013 to December 2015 at two tertiary oncology centers were reviewed. The diagnostic metrics of candidate constraints were computed by inverse probability of censoring weighting and compared using time-dependent receiver operating characteristic (ROC) curves with death designated as a competing event. Multivariable regression analyses were performed using the Fine–Gray sub-distribution hazard model.
Over a median follow-up period of 6.8 years, 205 (42.0 %) patients developed post-radiation primary hypothyroidism. The thyroid volume spared from 60 Gy (VS60) had the largest area under ROC curve of 0.698 at 5 years after radiotherapy. Of all evaluated constraints, VS60 at a cutoff value of 10 cc had the highest F-score of 0.53. The 5-year hypothyroidism risks of patients with thyroid VS60 ≥ 10 cc and < 10 cc were 14.7 % and 38.2 %, respectively (p < 0.001). The adjusted sub-hazard ratio for post-radiation primary hypothyroidism for VS60 < 10 cc was 1.87 (95 % confidence interval, 1.22–2.87; p < 0.001).
Thyroid VS60 is the best radiation dose–volume parameter to predict the long-term risk of primary hypothyroidism in patients with HNC who underwent neck irradiation. VS60 ≥ 10 cc is a robust constraint that limits the 5-year primary hypothyroidism risk to less than 15 % and should be routinely employed during radiotherapy optimization.
The low-mass X-ray binary (LMXB) system FIRST J102347.6+003841 hosts a newly born millisecond pulsar (MSP) PSR J1023+0038 that was revealed as the first and only known rotation-powered MSP in a ...quiescent LMXB. While the system is shown to have an accretion disk before 2002, it remains unclear how the accretion disk has been removed in order to reveal the radio pulsation in 2007. In this Letter, we report the discovery of Delta *g-rays spatially consistent with FIRST J102347.6+003841, at a significance of seven standard deviations, using data obtained by the Fermi Gamma-ray Space Telescope. The Delta *g-ray spectrum can be described by a power law (PL) with a photon index of 2.9 ? 0.2, resulting in an energy flux above 200 MeV of (5.5 ? 0.9) X 10--12 erg cm--2 s--1. The Delta *g-rays likely originate from the MSP PSR J1023+0038, but also possibly from an intrabinary shock between the pulsar and its companion star. To complement the Delta *g-ray study, we also re-investigate the XMM-Newton data taken in 2004 and 2008. Our X-ray spectral analysis suggests that a broken PL with two distinct photon indices describes the X-ray data significantly better than a single PL. This indicates that there exists two components and that both components appear to vary with the orbital phase. The evidence for Delta *g-ray emission conforms with a recent suggestion that Delta *g-rays from PSR J1023+0038 may be responsible for ejecting the disk material out of the system.
•Cancer risk in nasopharyngeal carcinoma survivors who underwent intensity-modulated radiotherapy was 90% higher than that in the general population.•Significant excess cancer risks were observed for ...oral cavity, sarcoma, oropharynx, paranasal sinus, salivary gland, thyroid, skin and lung.•Re-irradiation is an independent risk factor for in-field second primary cancer development.•Second primary cancer represents a significant cause of late mortality among NPC survivors.
Long-term risk of second primary cancer (SPC) after definitive intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) remains unclear. This study aims to evaluate the risk, predictive factors and survival impact of SPC in a large territory-wide cohort of NPC survivors in an endemic region.
In this multicenter study, consecutive NPC patients (n = 3166) who underwent definitive IMRT in all six public oncology centers in Hong Kong between 2001 and 2010 were included. SPC risks were quantified by standardized incidence ratios (SIRs) and absolute excess risks (AERs) estimated from corresponding age-, sex-, and calendar year-specific population cancer incidence data from the Hong Kong Cancer Registry. Predictive factors and SPC-specific mortality were analyzed.
Over a median follow-up period of 10.8 years, 290 cases of SPC were observed with a crude incidence of 9.2%. Cancer risk in NPC survivors was 90% higher than that in general population SIR, 1.9; 95% confidence interval (CI), 1.7–2.2, with an AER of 52.1 (95% CI, 36.8–67.3) per 10,000 person-years at risk. Significant excess cancer risks were observed for oral cavity, sarcoma, oropharynx, paranasal sinus, salivary gland, thyroid, skin and lung. Advanced age, smoking, hepatitis B status, and re-irradiation were independent predictive factors. SPC accounted for 9.4% of all deaths among NPC survivors during the study period, and 10-year SPC-specific mortality was 3.4%.
Second cancer risk after IMRT was substantial among NPC patients. SPC impairs long-term survival, and close surveillance is warranted as part of survivorship care.
Neuroblastoma (NB) is an embryonal tumor and possesses a unique propensity to exhibit either a spontaneous regression or an unrestrained growth. However, the underlying mechanism for this paradoxical ...clinical outcome remains largely unclear. Quantitative RT-PCR analysis on 102 primary NB tumors revealed that lower Krüppel-like factor 4 (KLF4) expression is frequently found in the unfavorable NB (Mann-Whitney test, P=0.027). In particular with the high-risk factors such as age of patient >1 year, MYCN amplification and low TRKA expression, the decreased expression of KLF4 was significantly associated with an unfavorable NB outcome. Despite knockdown of KLF4 alone is not sufficient to increase tumorigenicity of NB cells in vivo, stable expression of KLF4 short hairpin RNA in Be(2)-C cells significantly promoted growth of NB cells and inhibited cell differentiation toward fibromuscular lineage. In concordant with these observations, overexpression of KLF4 in SH-SY-5Y cells profoundly suppressed cell proliferation by direct upregulation of cell-cycle inhibitor protein p21(WAF1/CIP1), and knocking down p21(WAF1/CIP1) could partially rescue the suppressive effect of KLF4. Importantly, KLF4 overexpressing cells have lost their neuroblastic phenotypes, they were epithelial-like, strongly substrate-adherent, expressing smooth muscle marker and became non-tumorigenic, suggesting that KLF4 expression is crucial for lineage determination of NB cells, probably, favoring spontaneous tumor regression. Subsequent global gene expression profiling further revealed that transforming growth factor beta (TGFβ) and cell-cycle pathways are highly dysregulated upon KLF4 overexpression, and myogenic modulators, MEF2A and MYOD1 were found significantly upregulated. Taken together, we have demonstrated that KLF4 contributes to the favorable disease outcome by directly mediating the growth and lineage determination of NB cells.
The LORIS trial is an ongoing phase III clinical trial on low risk ductal carcinoma in situ (DCIS). DCIS patients aged ≥46 years with screen-detected low/intermediate nuclear grade were considered ...low risk and were randomised into surveillance or standard surgery. Here we review the 10-year territory-wide breast cancer registry database and evaluate the clinical outcomes of low versus high risk DCIS patients.
This was a retrospective study of a prospectively maintained territory-wide breast cancer registry in Hong Kong.
Between 1997 and 2006, 1391 DCIS patients were identified from the Hong Kong cancer registry breast cancer database. The mean age at diagnosis was 49.2 years (range 30–70). In total, 372 patients were classified as ‘low risk’, whereas the remaining 777 patients were classified as ‘high risk’. After a median follow-up of 11.6 years, the 10-year overall breast cancer-specific survival of the entire DCIS cohort was 1136/1149 (98.9%). Overall breast cancer-specific survival of low risk DCIS was 99.5%, whereas that in high risk DCIS was 98.6% (Log-rank test, P = 0.208).
Forty-six (12.4%) patients in the LORIS low risk group did not receive surgery, whereas 93 (12%) patients in the LORIS high risk group did not receive surgery. The 10-year breast cancer-specific survival in the non-operated low risk DCIS group was 97.8%; that in the non-operated high risk DCIS group was 96.7% (P = 1).
Long-term survival of DCIS was excellent, especially in low risk DCIS, regardless of surgical treatment.
•Incidence of ipsilateral invasive breast cancer event in patient with ductal carcinoma in situ (DCIS) was 759.4 in 100,000.•Incidence of subsequent invasive breast cancer in low-risk DCIS with or without surgery were comparable.•10-year overall breast cancer specific survival (BCSS) was 98.9%. Overall BCSS of LORIS-low risk and high-risk DCIS were comparable.•10-year BCSS in the non-operated low risk DCIS was 97.8%, and that in the non-operated high-risk DCIS was 96.7%.
A nearby superluminous burst GRB 130427A was simultaneously detected by six gamma -ray space telescopes (Swift, the Fermi GLAST Burst Monitor (GBM)/Large Area Telescope, Konus-Wind, SPI-ACS/INTEGRAL, ...AGILE, and RHESSI) and by three RAPTOR full-sky persistent monitors. The isotropic gamma -ray energy release is ~10 super(54) erg, rendering it the most powerful explosion among gamma-ray bursts (GRBs) with a redshift z < or =, slant 0.5. The emission above 100 MeV lasted about one day, and four photons are at energies greater than 40 GeV. We show that the count rate of 100 MeV-100 GeV emission may be mainly accounted for by the forward shock synchrotron radiation and the inverse Compton radiation likely dominates at GeV-TeV energies. In particular, an inverse Compton radiation origin is favored for the ~(95.3, 47.3, 41.4, 38.5, 32) GeV photons arriving at t ~ (243, 256.3, 610.6, 3409.8, 34366.2) s after the trigger of Fermi-GBM. Interestingly, the external inverse Compton scattering of the prompt emission (the second episode, i.e., t ~ 120-260 s) by the forward-shock-accelerated electrons is expected to produce a few gamma -rays at energies above 10 GeV, while five were detected in the same time interval. A possible unified model for the prompt soft gamma -ray, optical, and GeV emission of GRB 130427A, GRB 080319B, and GRB 090902B is outlined. Implications of the null detection of > 1 TeV neutrinos from GRB 130427A by IceCube are discussed.
PDF
