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We here present the first comprehensive provenance study of the Zambezi deep-sea fan, based on integrated petrographic, heavy-mineral, elemental-geochemistry, isotope-geochemistry, and detrital-zircon-geochronology analyses of middle Pleistocene to Holocene turbidites. The Zambezi Valley and Fan represent the submarine part of an ∼ 5000-km-long sediment-routing system, extending from the heart of the South African Plateau to the abyssal depths of the Indian Ocean. Sediment is derived not only from the African side, but also from Madagascar Island mostly via the Tsiribihina Valley. Being shed by two dissected rifted margins, detritus supplied from opposite sides of the Mozambique Channel shares similar feldspar-rich feldspatho-quartzose composition, although with significant differences in heavy-mineral and geochemical signatures. The εNd values of Madagascar sand are markedly more negative and TNd model ages notably older. Zircon grains yield mostly Irumide (late Stenian) U-Pb ages in African-derived sand and mostly Pan-African (Ediacaran–Cryogenian) U-Pb ages in Madagascar-derived sand, which also yields a few grains as old as Paleoarchean and many discordant ages reflecting Pan-African reworking of Archean cratonic rocks. Lower Valley and Lower Fan deposits have intermediate fingerprints, indicating that sediment supply from Madagascar is not much less than from Africa despite a much smaller catchment area, which can be explained by deposition of a conspicuous part of Africa-derived sediment in the Intermediate Basin confined between the Zambezi Shelf, the Beira High, and the Îles Éparses. By assuming that compositional differences between Quaternary submarine deposits and modern Zambezi River sands primarily resulted from sediment impoundment by large dams, we could evaluate the anthropogenic impact on natural sediment fluxes. Quaternary turbidites are somewhat higher in quartz and poorer in heavy minerals with higher relative amounts of durable ZTR species, and yield more Ediacaran, Neoarchean, and Carboniferous detrital-zircon ages than modern river sands. The Orosirian peak characterizing the Intermediate Basin sample points to prominent supply from the middle and upper parts of the Zambezi catchment in the middle Pleistocene. Rough calculations suggest that pre-dam Zambezi sediments were generated ≤ 10% in the upper catchment, ∼ 60% in the middle catchment, and only ≥ 30% in the lower catchment that provides the totality of sediment reaching the Indian Ocean today.

Elemental geochemistry, Nd isotopes, clay minerals, and U-Pb zircon ages integrated by petrographic and heavy-mineral data offer a multi-proxy panorama of mud and sand composition across the Zambezi sediment-routing system. Detrital-zircon geochronology highlights the four major episodes of crustal growth in southern Africa: Irumide ages predominate over Pan-African, Eburnean, and Neoarchean ages. Smectite, dominant in mud generated from Karoo basalts or in the equatorial/winter-dry climate of Mozambican lowlands, prevails over illite and kaolinite. Elemental geochemistry reflects quartz addition by recycling (Uppermost Zambezi), supply from Karoo basalts (Upper Zambezi), and first-cycle provenance from Precambrian basements (Lower Zambezi). Mildly negative for sediments derived from mafic granulites, gabbros, and basalts, åNd values are most negative for sand derived from cratonic gneisses. Intrasample variability among cohesive mud, very coarse silt, and sand is principally caused by the concentration of Nd-rich monazite in the fine tail of the size distribution. The settling-equivalence effect also explains deviations from the theoretical relationship between åNd and TNd,DM model ages, suggesting that monazite carries a more negative åNd signal than less dense and less durable heavy minerals. Elemental geochemistry and Nd isotopes reveal that the Mazowe-Luenha river system contributes most of the sediment reaching the Zambezi Delta today, with minor supply by the Shire River. Sediment yields and erosion rates are lower by an order of magnitude on the low-relief Kalahari Plateau than in rugged Precambrian terranes. On the Plateau, mineralogical and geochemical indices testify to extensive breakdown of feldspars and garnet unjustified by the presently dry climate. Detrital kaolinite is recycled by incision of Cretaceous- Cenozoic paleosols even in the wetter lower catchment, where inefficient hydrolysis is testified by abundant fresh feldspars and undepleted Ca and Na. Mud geochemistry and surficial corrosion of ferromagnesian minerals indicate that, at present, weathering increases only slightly downstream the Zambezi River.

Deserts are virtually the largest exposed sand depository on earth and their interaction with the river network may unveil information of present and past routing systems. Provenance studies of Sahara, Kalahari Deserts intend to apply common petrographic, geochemical and isotopic analysis to propose suggestive sedimentological information of dryland areas.The mineralogical composition of aeolian dunes and its variability across a sand sea reflect the relative importance of fluvial and aeolian processes and the degree of their interplay. Sand seas largely fed by river systems are typically characterized by partly first-cycle detritus including various amounts of diverse types of rock fragments, feldspars and heavy minerals, generally allowing identification of a single dominant source. The opposite end member is represented by dunefields where sand is dominantly generated in situ from disaggregation of locally exposed rocks with high sand-generation potential (e.g., quartz-rich sandstones) and next reworked and homogenized by winds during several sedimentary cycles. In these cases, sand typically bears a distilled homogenous composition consisting almost exclusively of mostly rounded monocrystalline quartz associated with an extremely poor tHM suite dominated by durable ZTR minerals, as for the Sahara Desert (Pastore et al., 2021).The Kalahari Basin, which extends over twenty degrees of latitude, is characterized by a pronounced increase in precipitation from the southwest to the subequatorial north and has seen repeated changes in climatic conditions through the recent and less recent past, provides both end-member examples, as well as a series of intermediate situations. Sand mineralogy is rather homogeneously pure quartzose in the north, closer to humid equatorial regions, but presents peculiar feldspar-rich or even lithic-rich compositions at both western and eastern margins of the erg, where detrital modes with more abudant and varied tHM suites indicate largely first-cycle supply from local rivers (Garzanti et al., 2022) . The evidence shows that a better developed fluvial network can interrupt the “recycling factory” of the desert, introducing first cycle eroded sediment deflated from river flanks into the dunes.The geographic distribution of such contrasting desert types is mainly controlled by precipitation in adjacent highlands fueling fluvial discharge. In hyper-arid tropical deserts dominated by aeolian dynamics, such as the Sahara, river action may be weakened to the point that fluvial supply to the aeolian system becomes insignificant. Fluvial sources are instead readily identified for dunefields accumulated in drylands at the foot of high mountain areas, as in Kalahari flanks or central Asia and Argentina (e.g., Rittner et al., 2016, Garzanti 2020, 2021).Pastore, G., et al., 2021. Provenance and recycling of Sahara Desert sand. Earth-Science Reviews, 216.Garzanti, E., et al., 2022. Provenance of Kalahari Sand: Paleoweathering and recycling in a linked fluvial-aeolian system. Earth-Science Reviews, 224.Rittner, M., et al., 2016. The provenance of Taklamakan desert sand. Earth and Planetary Science Letters, 437.Garzanti, E., et al., 2020. Provenance of Thal Desert sand: Focused erosion in the western Himalayan syntaxis and foreland-basin deposition driven by latest Quaternary climate change. Earth-Science Reviews, 207.Garzanti, E. et al., 2021. Transcontinental retroarc sediment routing controlled by subduction geometry and climate change (Central and Southern Andes, Argentina). Basin Research, 33.

We here review what is known about the dunefields and fluvial systems of the Kalahari Basin in terms of geological setting and Quaternary dynamics and set out what has been hypothesized about the provenance of Kalahari sand so far. Previous work has tackled this problem by applying a limited number of techniques (mostly sediment textures and heavy minerals) to parts of the large dryland. The generally highly quartzose mineralogy of aeolian dunes and their compositional variability have been only broadly evaluated and several sedimentological issues have thus remained controversial, including the relative role played by fluvial processes versus aeolian reworking of older sediments and weathering controls. This reveals a need for a systematic provenance study that considers the entire basin. For this reason, here we combine original petrographic, heavy-mineral, and detrital-zircon geochronology data with previously published clay-mineral, geochemical, and geochronological information to present the first comprehensive provenance study of the vast Kalahari sand sea. Our multi-proxy dataset comprises 100 samples, collected across the Kalahari Basin from 11°S (NW Zambia) to 28°S (NW South Africa) and from 15°E (Angola) to 28°30′W (Zimbabwe). Kalahari aeolian-dune sand mostly consists of monocrystalline quartz associated with durable heavy minerals and thus drastically differs from coastal dunefields of Namibia and Angola, which are notably richer in feldspar, lithic grains, and chemically labile clinopyroxene. The western Kalahari dunefield of southeastern Namibia is distinguished by its quartz-rich feldspatho-quartzose sand, indicating partly first-cycle provenance from the Damara Belt and Mesoproterozoic terranes. Within the basin, supply from Proterozoic outcrops is documented locally. Composition varies notably at the western and eastern edges of the sand sea, reflecting partly first-cycle fluvial supply from crystalline basements of Cambrian to Archean age in central Namibia and western Zimbabwe. Basaltic detritus from Jurassic Karoo lavas is dominant in aeolian dunes near Victoria Falls. Bulk-sediment petrography and geochemistry of northern and central Kalahari pure quartzose sand, together with heavy-mineral and clay-mineral assemblages, indicate extensive recycling via aeolian and ephemeral-fluvial processes in arid climate of sediment strongly weathered during previous humid climatic stages in subequatorial Africa. Distilled homogenized composition of aeolian-dune sand thus reverberates the echo of paleo-weathering passed on to the present landscape through multiple episodes of fluvial and aeolian recycling. Intracratonic sag basins such as the Kalahari contain vast amounts of quartz-rich polycyclic sand that may be tapped by rivers eroding backwards during rejuvenation stages associated with rift propagation. Such an event may considerably increase the sediment flux to the ocean, fostering the progradation of river-fed continental-embankments, as documented by augmented accumulation rates coupled with upward increasing mineralogical durability in the post-Tortonian subsurface succession of the Zambezi Delta. The Central Kalahari is not a true desert. It has none of the naked, shifting sand dunes that typify the Sahara and other great deserts of the world. In some years the rains may exceed twenty — once even forty — inches, awakening a magic green paradise.” Mark Owens, Cry of the Kalahari.

The Zambezi River rises at the center of southern Africa, flows across the low-relief Kalahari Plateau, meets Karoo basalt, plunges into Victoria Falls, follows along Karoo rifts, and pierces through Precambrian basement to eventually deliver its load onto the Mozambican passive margin. Reflecting its polyphase evolution, the river is subdivided into segments with different geological and geomorphological character, a subdivision finally fixed by man’s construction of large reservoirs and faithfully testified by sharp changes in sediment composition. Pure quartzose sand recycled from Kalahari desert dunes in the uppermost tract is next progressively enriched in basaltic rock fragments and clinopyroxene. Sediment load is renewed first downstream of Lake Kariba and next downstream of Lake Cahora Bassa, documenting a stepwise decrease in quartz and durable heavy minerals. Composition becomes quartzo-feldspathic in the lower tract, where most sediment is supplied by high-grade basements rejuvenated by the southward propagation of the East African rift. Feldspar abundance in Lower Zambezi sand has no equivalent among big rivers on Earth and far exceeds that in sediments of the northern delta, shelf, and slope, revealing that provenance signals from the upper reaches have ceased to be transmitted across the routing system after closure of the big dams. This high-resolution petrologic study of Zambezi sand allows us to critically reconsider several dogmas, such as the supposed increase of mineralogical “maturity” during long-distance fluvial transport, and forges a key to unlock the rich information stored in sedimentary archives, with the ultimate goal to accurately reconstruct the evolution of this mighty river flowing across changing African landscapes since the late Mesozoic.

The Sahara is by far the largest hot desert on Earth. Its composite structure includes large dune fields hosted in sedimentary basins separated by elevated areas exposing the roots of Precambrian orogens or created by recent intraplate volcanism. Such an heterogeneity of landscapes and geological formations is contrasted by a remarkably homogeneous composition of dune sand, consisting almost everywhere of quartz and durable minerals such as zircon, tourmaline, and rutile.We here present the first comprehensive provenance study of the Sahara Desert using a combination of multiple provenance proxies such as bulk-petrography, heavy-mineral, and detrital-zircon U–Pb geochronology. A set of statistical tools including Multidimensional Scaling, Correspondence Analysis, Individual Difference Scaling, and General Procrustes Analysis was applied to discriminate among sample groups with the purpose to reveal meaningful compositional patterns and infer sediment transport pathways on a geological scale.Saharan dune fields are, with a few local exceptions, composed of pure quartz with very poor heavy-mineral suites dominated by durable zircon, tourmaline, and rutile. Some more feldspars, amphibole, epidote, garnet, or staurolite occur closer to basement exposures, and carbonate grains, clinopyroxene and olivine near a basaltic field in Libya. Relatively varied compositions also characterize sand along the Nile Valley and the southern front of the Anti-Atlas fold belt in Morocco. Otherwise, from the Sahel to the Mediterranean Sea and from the Nile River to the Atlantic Ocean, sand consists nearly exclusively of quartz and durable minerals. These have been concentrated through multiple cycles of erosion, deposition, and diagenesis during the long period of relative tectonic quiescence that followed the Neoproterozoic Pan-African orogeny, the last episode of major crustal growth in the region. The principal ultimate source of recycled sand is held to be represented by the thick blanket of quartz-rich sandstones that were deposited in the Cambro-Ordovician from the newly formed Arabian-Nubian Shield in the east to Mauritania in the west.The composition and homogeneity of Saharan dune sand reflects similar generative processes and source rocks, and extensive recycling repeated through geological time after the end of the Neoproterozoic, which zircon-age spectra indicate as the last major event of crustal growth in the region. The geographic zircon-age distribution in daughter sands thus chiefly reflects the zircon-age distribution in parent sandstones, and hence sediment dispersal systems existing at those times rather than present wind patterns. This leads to the coclusion that, provenance studies based on detrital-zircon ages, the assumption that observed age patterns reflect transport pathways existing at the time of deposition rather than inheritance from even multiple and remote landscapes of the past thus needs to be carefully investigated and convincingly demonstrated rather than implicitly assumed.

U Pb zircon geochronology is one of the most widely used techniques in sedimentary provenance analysis. Unfortunately, the ability of this method to identify sediment sources is often degraded by sediment recycling and mixing of detritus from different source rocks sharing similar age signatures. These processes create non-unique zircon U Pb age signatures and thereby obscure the provenance signal. We here address this problem by combining detrital zircon U Pb geochronology with Raman spectroscopy. The position and width of the Raman signal in zircon scales with its degree of metamictization, which in turn is sensitive to temperature. Thus, combined U-Pb + Raman datasets encode information about the crystallization history of detrital zircons as well as their thermal history. Using three borehole samples from Mozambique as part of a source-to-sink study of interest for hydrocarbon exploration, we show that zircon populations with similar U Pb age distributions can exhibit different Raman signatures. The joint U-Pb + Raman analysis allowed us to identify three different annealing trends, which were linked to specific thermal events. Thus we were able to differentiate a dominant Pan-African U Pb age peak into several sub-populations and highlight the major effect of Karoo tectono-magmatic events. In our case study, we used Raman also as a means to systematically identify all zircon grains in heavy-mineral mounts, resulting in considerable time savings. Raman spectroscopy is a non-destructive and cost-effective method that is easily integrated in the zircon U Pb dating workflow to augment the resolution power of detrital zircon U Pb geochronology.

We here present the first comprehensive provenance study of the Sahara Desert using a combination of multiple provenance proxies and state-of-the-art statistical analysis. Our dataset comprises 44 aeolian-dune samples, collected across the region from 12°N (Nigeria) to 34°N (Tunisia) and from 33°E (Egypt) to 16°W (Mauritania) and characterized by bulk-petrography, heavy-mineral, and detrital-zircon U Pb geochronology analyses. A set of statistical tools including Multidimensional Scaling, Correspondence Analysis, Individual Difference Scaling, and General Procrustes Analysis was applied to discriminate among sample groups with the purpose to reveal meaningful compositional patterns and infer sediment transport pathways on a geological scale. The overall homogenity across sand samples, however, precluded a detailed narrative. Saharan dune fields are, with a few local exceptions, composed of pure quartzose sand with very poor heavy-mineral suites dominated by durable zircon, tourmaline, and rutile. Some feldspars, amphibole, epidote, garnet, or staurolite occur closer to basement exposures, and carbonate grains, clinopyroxene and olivine near a basaltic field in Libya. Relatively varied compositions also characterize sand along the Nile Valley and the southern front of the Anti-Atlas fold belt in Morocco. Otherwise, from the Sahel to the Mediterranean Sea and from the Nile River to the Atlantic Ocean, sand consists nearly exclusively of quartz and durable minerals. These have been concentrated through multiple cycles of erosion, deposition, and diagenesis of Phanerozoic siliciclastic rocks during the long period of relative tectonic quiescence that followed the Neoproterozoic Pan-African orogeny, the last episode of major crustal growth in the region. The principal ultimate source of recycled sand is held to be represented by the thick blanket of quartz-rich sandstones that were deposited in the Cambro-Ordovician from the newly formed Arabian-Nubian Shield in the east to Mauritania in the west. Durability of zircon grains and their likelihood to be recycled from older sedimentary rocks argues against the assumption, too often implicitly taken for granted in provenance studies based on detrital-zircon ages, that their age distribution reflects transport pathways existing at the time of deposition rather than inheritance from multiple and remote landscapes of the past.

BACKGROUND Several nonbiological factors, including socioeconomic status indicators and other family characteristics, influence survival from childhood cancers. Our study explores the association between parental education and childhood cancer survival. METHODS The specialized Childhood Cancer Registry of the Piedmont region in Italy provided data on all the cases (aged 0-14) diagnosed with cancer in the period 1976-2011 who resided in the city of Turin (capital of the Piedmont region) at least once since 1971. Information on parental education was extracted from the Turin Longitudinal Study by record linkage. The association between parental educational level and survival was estimated using Cox regression. RESULTS The study included 949 children. We observed a disadvantage in the overall survival for children of less educated mothers. No such effect was observed for paternal education. The effect of maternal education was particularly strong for central nervous system tumors (hazard ratios, 2.9; 95% confidence interval, 1.1-8.0). A similar effect, though smaller in magnitude, was observed for leukemia and embryonal tumors, whereas the estimates for lymphoma were imprecise. CONCLUSIONS Our study shows an association between maternal educational level and survival in children with central nervous system tumors, a diagnosis that often requires long-lasting treatment and special care. Giving support to the families of affected children to provide them the optimal care has the potential to improve children's cancer treatment outcomes.

Bare electrodynamic tethers are proposed in the recent literature as a potential solution for deorbiting large dual-payload adapters, such as Sylda onboard Ariane 5. Deorbit measures are required to mitigate the increase of debris population, and consequent collision risk, in space. The system proposed hereby is made of two bare electrodynamic tethers (BET), deployed with respective tip-masses, along opposite directions from Sylda, after its release in GTO at apogee. This paper investigates the design, optimization and simulation of a vision system to detect the position over time of the tip-masses during deployment. A representative deployment profile is used to select the vision system and optimize its key features, such as the focal length and the number of cameras. This design will also account for minimum cost and small size, that are crucial drivers for deorbit applications.

Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height ( 180 cm) vs. short (

Background The results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long-term survival can be expected, but late events are known to occur. We analyzed the long-term results of the RMS 79 protocol to investigate the type and impact of such events. Procedure From 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow-up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone. Results Overall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment-related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long-term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group. Conclusions Major late events can significantly affect the long-term survival of children with RMS. Modern protocols should provide for a much longer follow-up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated. Pediatr Blood Cancer 2012; 58: 872–876. © 2011 Wiley Periodicals, Inc.

Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries. Standardized incidence ratios (SIRs) with 95% confidence intervals (CI) and cumulative incidence of second malignancies were computed. We observed 175 second malignant neoplasms, yielding a SIR of 4.6, 95% CI: 3.9-5.3. When considering second cancers with at least 10 occurrences, highest relative risks were found for second malignant bone tumors (SIR = 26.4, 16.6-40.0), soft tissue sarcomas (SIR = 14.1, 6.7-25.8) and myeloid leukemia (SIR = 12.7, 6.3-22.8). Significant increased risks for all malignancies combined were observed after sympathetic nervous system tumors (SIR = 11.4, 5.2-21.6), retinoblastomas (SIR = 7.3, 5.4-9.8), renal tumors (SIR = 5.7, 3.8-8.0), malignant bone tumors (SIR = 5.6, 3.7-8.2), soft tissue sarcomas (SIR = 4.7, 3.2-6.8), germ-cell, trophoblastic and other gonadal neoplasms (SIR = 2.5, 1.1-4.9), carcinomas and other malignant epithelial neoplasms (SIR = 2.2, 1.4-3.3). The highest risk of a second malignancy of any type occurred 5 to 9 years after NCNSSC (SIR = 9.9, 6.8-13.9). The cumulative incidence of second malignancies 10 years after the first neoplasm was eight times higher among NCNSSC survivors than in the general population, with the absolute difference between observed and expected cumulative incidence still increasing after 50 years of follow-up. Children who survived a NCNSSC experience a large increased risk of developing a new malignancy, even many years after their initial diagnosis. Copyright © 2011 UICC.

BACKGROUND: In many types of cancer, the survival rates are reported to be less favorable for adolescents compared with younger children. To investigate whether this is true for adolescents with rhabdomyosarcoma (RMS), the results obtained in patients enrolled in protocols run by the Italian Soft Tissue Sarcoma Committee (STSC) were analyzed. METHODS: From 1988 through 2005, 643 patients were registered (567 children ages birth-14 years and 76 adolescents ages 15-19 years) and treated in 4 STSC protocols. The number of patients enrolled was compared with the expected number calculated from incidence rates derived from the Italian network of cancer registries. RESULTS: Only 27% of the expected number of adolescents with RMS were enrolled in the STSC trials. Compared with children, adolescents were found to have a longer interval from initial symptoms to diagnosis (8 weeks vs 4.6 weeks), more alveolar RMS (47.4% vs 32.6%), lymph node infiltration (39.1% vs 23.3%), and metastases at the time of diagnosis (30.7% vs 17.8%). The 2 age groups received similar treatments. The 5-year overall survival (OS) rate was 68.9% in children versus 57.2% in adolescents (P = .006), and the progression-free survival (PFS) rate was 64.3% in children versus 48.1% in adolescents (P = .0237). On multivariate analysis, age, tumor site, lymph node involvement, and metastases were found to be significant prognostic factors for OS and PFS. CONCLUSIONS: Survival for adolescents with RMS enrolled in STSC protocols appears to be satisfactory. The higher prevalence of unfavorable tumor characteristics noted among adolescents seems to explain their worse outcome compared with children. However, the limited number of adolescents enrolled in STSC studies is worrisome, and cooperation with oncologists who treat adults needs to be improved. Cancer 2012;. © 2011 American Cancer Society.

BACKGROUND: Colorectal cancer is exceedingly rare in children and adolescents. Reports from small series indicate that poor prognostic factors are more common in children than in adults, resulting in worse outcome for the pediatric population. METHODS: The Surveillance, Epidemiology, and End Results database was searched for records of children/adolescents with colorectal cancer, and the features and outcomes were compared with those of adults. RESULTS: From January 1973 through December 2005, only 159 children/adolescents (ages 4-20 years) were reported with a diagnosis of colorectal cancer. The most common sites of involvement were the rectum (27%) and the transverse colon (26%). Adenocarcinoma was the most common histiotype in both adults and pediatric patients; however, children/adolescents had more unfavorable histiotypes (ie, mucinous adenocarcinoma [22%] and signet ring cell carcinoma [18%]) when compared with adults (10% and 1%, respectively; P < .001). Poorly differentiated and undifferentiated tumors (grades III and IV, respectively) and distant stage were more common in children/adolescents (P < .001). The 5-year relative survival estimates in children/adolescents and adults were 40% ± 4.2% and 60% ± 0.10%, respectively, confirming a worse outcome in the pediatric age group (P < .001). CONCLUSIONS: Children/adolescents represent a minority of patients with colorectal cancer and have high-risk features and worse outcome than adults. The small number of patients in this age group was an impediment to the development of meaningful clinical trials. Thus, the principles of management for adult colorectal cancer should be used in the treatment of children and adolescents. Cancer 2010. © 2009 American Cancer Society.

Rare malignant pediatric tumors are essentially orphan diseasesand make up a variety of neoplasms with particular biological andclinicalcharacteristics.Someofthesetumorsarerareatanyage,butmost are particularly rare in childhood and adolescence [1].In 2000, a nationwide Italian cooperative project, called theTREP (Tumori Rari in Eta` Pediatrica or Rare Tumours in PediatricAge) project, was launched in Italy under the auspices of theAssociazione Italiana Ematologia Oncologia Pediatrica (AIEOP),and in cooperation with the Societa` Italiana Chirurgia Pediatrica(SICP) to improve basic research on these tumors and their clinicalmanagement. The project aimed to establish a network of pediatricand adult oncologists, surgeons, pathologists and biologists, to poolclinical data, and develop diagnostic and therapeutic recommenda-tions for each of these rare tumors [2].As a first step, the TREP group gave an arbitrary but pragmaticdefinition of ‘‘rare pediatric tumors,’’ defining them as solidmalignancies characterized by annual incidence rates of less than2 per million children (0–14 years) and not enrolled in specificclinical trials. The list included: nasopharyngeal carcinoma,adrenocortical tumors, pleuro-pulmonary blastoma (and other lungtumors), carcinoid tumors, cutaneous melanoma, renal carcinoma,pancreatoblastoma (and other pancreatic exocrine tumors), gonadalnon-germ-cell tumors (ovary/testis), pheochromocytoma and para-ganglioma, thyroid carcinoma, salivary gland tumors, breastcarcinoma, carcinoma of the gastrointestinal tract, and carcinomaof the thymus [2]. Therefore, the list excluded entities as renalrhabdoid tumors, that are registered in the national Wilms study;hepatoblastomaandmalignantgermcelltumors,thathavetheirownprotocols; rare histotypes of soft part sarcomas, that are covered bythe cooperative study on soft tissue sarcomas, as well as rare bonetumors; and other tumors whose incidence parallels that of rarepediatric tumors butwere already included in clinical trials. Centralnervous system tumors and hematological malignancies wereexcluded from the TREP list.TheTREPgrouphasalreadypublishedareportonitsfirst6yearsof activity. Here, we compare the number of these rare pediatrictumors expected to be diagnosed in Italy (based on incidence datafrom Italian network of well-established population-based cancerregistries [AIRTum]) [3] and the number of patients enrolled in theTREP project between 2000 and 2006, with a view to appraisingthe nationwide diffusion and efficacy of the TREP project. Thestudy analyzed the differences in the patterns of referral of children(0–14 years old) and adolescents less than 18 years (15–17 yearsold) with rare malignant tumors.

This population-based study (the largest on this issue conducted in Southern Europe) has examined mortality among the parents of 2622 children diagnosed with cancer in Piedmont during 1967-1994. Parents were followed up from the date of the index child's birth until the end of 2000, yielding a total of 118 090.7 person-years of observation. Standardized mortality ratios (SMRs) were estimated using mortality rates for the whole population of Piedmont as the reference. Among mothers, total mortality was similar to that expected [SMR 1.02, 95% confidence interval (CI) 0.85-1.23, 117 cases]. A reduced risk of mortality was seen in fathers (SMR 0.91, 95% CI 0.81-1.02, 293 cases); this was largely due to causes other than cancer and the reduction in risk disappeared after the index child's death (SMR 0.98, 95% CI 0.84-1.15, 168 cases). Deaths from cancers of the lymphohaematopoietic system were in excess among mothers (SMR=2.13, 95% CI 1.02-3.92, 10 cases) and breast cancer deaths were in excess specifically among mothers of leukaemic children (SMR 2.32, 95% CI 1.16-4.14, 11 cases). Three mothers dying with breast cancer had index children who had been diagnosed with a bone sarcoma. Parental cancer of the respiratory tract was significantly associated with both tumours of the central nervous system and Hodgkin's lymphoma in the index child. The excess risks identified here may be due to genetic factors or due to parental psychological stress consequent to cancer in a child that may lead to increased mortality either through the direct effects of stress or through consequent changes in lifestyle.

Background A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM). Procedures Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1–2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. Results All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7–14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. Conclusions High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated. Pediatr Blood Cancer 2008;50:537–541. © 2007 Wiley-Liss, Inc.

Background: Survivors of childhood leukemia and lymphoma experience high risks of second malignant neoplasms. We quantified such risk using a large dataset from 13 population-based cancer registries. Methods: The registries provided individual data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring in children aged 0-14 years and on subsequent second malignant neoplasms for different time periods from 1943 to 2000. Risks of second malignant neoplasms were assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs), using the incidence rates in the general populations covered by the registries as a reference. Cumulative absolute risks were also calculated. Results: A total of 133 second malignant neoplasms were observed in 16 540 patients (12 731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin lymphomas) after an average follow-up of 6.5 years. The most frequent second malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% CI = 5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% CI = 4.30 to 17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% CI = 8.60 to 35.7); the most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5, 95% CI = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% CI = 7.66 to 45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% CI = 12.5 to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer (six cases, SIR = 40.4, 95% CI = 14.8 to 88.0) and brain cancer (four cases, SIR = 6.97, 95% CI = 1.90 to 17.9). Cumulative incidence of any second malignant neoplasm was 2.43% (95% CI = 1.09 to 3.78), 12.7% (95% CI = 8.29 to 17.2), and 2.50% (95% CI = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, respectively. Conclusions: This population-based study provides, to our knowledge, the most precise and up-to-date estimates for relative and absolute risks of second malignant neoplasms after childhood leukemia and lymphoma. © The Author 2007. Published by Oxford University Press. All rights reserved.

Risk factors of central venous lines-related thrombosis in children with acute lymphoblastic leukemia during induction therapy: a prospective study

We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggested for TTN (genes affecting lung liquid clearance). Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely.

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).

Survival after childhood cancer has been improving since the late 1970s in most developed countries. The Childhood Cancer Registry of Piedmont has been recording malignant tumors in children (0-14 years) throughout Piedmont since 1967. The present paper is based on the records of the 2,970 children diagnosed during the period 1970-2001; survival rates are estimated up to June 30, 2004. Based on records from the Registrar Offices of the relevant towns of residence, 1,698 children were reported to be alive, 1,252 deceased, and 20 were of unknown vital status. Over the period 1970-2001, 5-year survival rates for all tumor types combined showed a statistically significant increasing trend (p

This paper describes the database of children with cancer in the EUROCARE study and the methodology used to analyse and report survival. This is the first systematic evaluation of survival after childhood cancer on a large scale in Europe: approximately 45 000 cases were included, diagnosed between 1978 and 1992 (34 814 cases diagnosed in 1978–1989 and an additional set of 9495 cases diagnosed in 1990–1992) and followed-up until 1995. Data were provided from 34 population-based registries (four specialised for childhood cancer registrations and one specialised registry for childhood leukaemia) in 17 countries of Europe (where there was national coverage in 10 countries). Quality of the data was fairly good, given the general differences among the countries and their health systems, thereby allowing for comparisons between them. Among cases diagnosed in 1978–1989, overall 2.0% were lost to follow-up, 91.8% were microscopically diagnosed and 93.4% of alive cases had at least 5 years of observation. Survival proportions (observed survival) were calculated for each of the countries involved, by age group (0, 1–4, 5–9, 10–14 years), gender, different time periods and selected diagnostic groups. Age-standardised cumulative survival rates and European averages (weighted and pooled) were also computed. Cox regression models were used to evaluate geographical and temporal differences. The EUROCARE database represents a unique source of information on survival of childhood cancer patients in Europe, intercountry differences and time trends in survival.

Aims and Background A cohort study was conducted in order to measure cause-specific mortality among parents of children recorded in the Childhood Cancer Registry of Piedmont. It is the first study carried out on the subject in southern Europe. Methods and Study Design The study comprised the 740 children resident in Turin and in whom a cancer had been diagnosed in the period 1967-1991. Nominal data were obtained for 723 fathers and 733 mothers. At the end of the follow-up in 1995, 645 fathers were alive, 68 dead and 10 untraceable. Corresponding figures for mothers were 700, 28 and 5. Cause of death was known for 91 of 96 parents. Results The period of observation of parents started on the birth of the index child, however mortality analyses were restricted to the period after 1965 because of limited availability of local reference rates. Total mortality was lower than expected among fathers (66 observed deaths vs 88.2 expected, P Conclusions The data do not indicate any increase in mortality from cancer or other causes and, on the contrary, show a reduction in mortality which was more evident for the causes related to life style.

High incidence of acute promyelocytic leukemia in children in northwest Italy, 1980–2003: a report from the Childhood Cancer Registry of Piedmont

The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1–86 mo) and followed over 10 years (median 60 mo; range 1–232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy. © 1995 Wiley-Liss, Inc.

The results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long-term survival can be expected, but late events are known to occur. We analyzed the long-term results of the RMS 79 protocol to investigate the type and impact of such events.From 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow-up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone.Overall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment-related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long-term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group.Major late events can significantly affect the long-term survival of children with RMS. Modern protocols should provide for a much longer follow-up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated.

Background To describe late sequelae and their correlation with presenting clinical features and tumor treatment in children with symptomatic epidural compression (EC) secondary to localized neuroblastoma. Procedures A total of 98 evaluable children diagnosed with neuroblastoma and EC, who survived a minimum of 2 years were identified in two Italian and French neuroblastoma series. Results Symptoms of EC at diagnosis included motor deficit in 94 cases and sphincter deficits in 33. Initial treatment was chemotherapy in 66 cases, neurosurgical decompression in 29 and radiotherapy in 3. Chemotherapy was chosen more frequently for younger children and for those with stage 3 disease. Overall treatment consisted of chemotherapy alone in 44 cases, neurosurgery and chemotherapy in 38, radiotherapy and chemotherapy, with or without neurosurgery, in 16. After a median follow-up of 7.3 years, 57 children (58.2%) had one or more sequelae. Motor sequelae involved 50/57 of these children and correlated with age and severity of motor deficit at diagnosis and neurosurgical treatment. Spine deformities involved 27/57 children and were more frequent in those with severe motor deficit at diagnosis, or who were treated by neurosurgery or radiotherapy. Sphincter dysfunctions involved 31/57 children and were more frequent among children who presented with sphincter symptoms and severe motor deficit. Conclusions Fifty-eight percent of the children with localized neuroblastoma and symptomatic EC registered in this study developed late sequelae. The severity of motor deficit at diagnosis was the main risk factor. Pediatr Blood Cancer 2011; 57: 473–480. © 2011 Wiley-Liss, Inc.

Purpose To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma. Patients and Methods The study includes data from 2,216 children (age 0 to 14 years) diagnosed between 1979 and 2005. Overall survival (OS) was analyzed by clinical and biologic features at presentation and periods of diagnosis: 1979 to 1984, 1985 to 1991, 1992 to 1998, and 1999 to 2005. The relative risk of second malignant neoplasm (SMN) was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent. Results Yearly patient accrual increased over time from 58 to 102. Patients age 0 to 17 months represented 45.6% of the total population, and their incidence increased over time from 36.5% to 48.5%. The incidence of stage 1 patients increased over time from 5.8% to 23.2%. A total of 898 patients (40.5%) developed disease progression or relapse, 19 patients developed SMN, and two patients developed myelodysplasia. The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8.4 (95% CI, 5.1 to 13.2). A total of 858 patients (39%) died (779 of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications). Ten-year OS was 55.3% (95% CI, 53.0% to 57.6%) and increased over time from 34.9% to 65.0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%), but not afterward. Conclusion The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN.

The majority of childhood cancer cases survive to adulthood. We describe the experience of marriage and reproduction as indicators of quality of life, in a population-based cohort of adult long-term survivors after early cancer reported to the Childhood Cancer Registry of Piedmont. The study included 1237 survivors with a malignant neoplasm diagnosed during 1967-2000 when aged 0-14 years, who attained age 18 years. Vital and marital status and number of offspring were assessed through the Vital Statistics Offices. Marriage and fertility deficits were estimated by comparison with the Piedmont population. Among the individuals included in this study, 919 (74.3%) never married and never lived as married. The marriage deficit was 32% [observed/expected 0.68; 95% confidence interval (CI): 0.55-0.83] in men and 18% (observed/expected 0.82; 95% CI: 0.68-0.98) in women. A total of 179 children were born to 120 women, with a fertility deficit of 41% (observed/expected 0.59; 95% CI: 0.51-0.69). In conclusion, the observed decrements in marriage in men and women and fertility in women suggest that efforts should be made to improve the recovery from physical and psychological traumas related to diagnosis and treatment of cancer.

A national project focusing on rare malignant pediatric tumors (the TREP project) was launched in Italy in 2000. The present study compared the number of these tumors expected to be diagnosed in Italy with the number of cases actually enrolled in the TREP database in 2000-2006.The predicted number of cases was calculated from incidence data from the Italian network of cancer registries (AIRTum).The TREP database included 336 patients under 18 years, that is, 261 children and 75 adolescents, as compared to 305 and 400 expected cases, respectively. For the 0-14 years old age-group, the ratio of observed to expected cases was 1:1 for nasopharyngeal carcinoma, adrenocortical tumors, renal cell carcinoma, and gonadal non-germ-cell tumors, while for the 15-17-year old individuals there was a statistically significant under-reporting for all tumor types.Our study showed that the TREP project succeeded in registering and treating the vast majority of the patients under 15 years of age with rare pediatric tumors, demonstrating the feasibility of cooperative protocols even for rare diseases. Conversely, there was a large gap between those registered compared to those expected for adolescents.

Purpose: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. Methods: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. Results: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). Conclusion: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour. © 2008 Elsevier Ltd. All rights reserved.

A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM).Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period.All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression.High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.

Aim of the study To determine the Health Related Quality of Life (HRQL) in a population-based cohort of long-term survivors of childhood cancer in Piedmont, northwestern Italy. Patients and methods During 2003, a 15-item Health Utilities Index questionnaire was mailed to 1005 5-year survivors, identified from the population-based Childhood Cancer Registry of Piedmont, to derive scores for overall HRQL and for eight single attributes of health. Score differences were estimated as adjusted prevalence odds ratios. Results A large majority of long-term survivors had moderately high scores for overall HRQL and for each of the single attributes. Males reported better overall HRQL and less morbidity with respect to dexterity, emotion and pain than females. Survivors diagnosed when they were 10–14 years of age had better overall HRQL and less morbidity with respect to emotion, cognition and pain than younger persons. Long-term survivors of central nervous system (CNS) tumours, retinoblastoma and bone tumours had greater impairment of overall HRQL, vision, ambulation, dexterity, cognition and pain than survivors of other forms of cancer. Conclusion Many survivors of childhood cancer in Piedmont had fairly good overall HRQL. Greater probability of impaired HRQL was seen for females, survivors of CNS tumours, retinoblastoma and bone tumours, and persons diagnosed before 10 years of age.

The aim of this study was to compare the characteristics of respondents and nonrespondents in a survey of childhood cancer survivors recorded in the Childhood Cancer Registry of Piedmont and their current primary care general practitioners. Eligible subjects were identified from the Childhood Cancer Registry of Piedmont and the referring general practitioners were traced through the National Health Service. A postal questionnaire was sent both to childhood cancer survivors and to their general practitioners. Prevalence odds ratios were estimated for demographic and clinical characteristics in survivors and for demographic characteristics in general practitioners. A total of 1005 childhood cancer survivors and 857 general practitioners (132 of them had two or more cancer survivors in care) were included in the study. Completed questionnaires were obtained from 691 survivors (69%) and 615 general practitioners (72%). For survivors, the only associations with nonresponse were for age 35-44 years [prevalence odds ratio: 0.53 (95% confidence interval: 0.33-0.85)], being married [prevalence odds ratio: 1.45 (95% confidence interval: 0.96-2.18)] and diagnosis after 1977 [prevalence odds ratio: 0.66 (95% confidence interval: 0.42-1.03)]. For general practitioners, the only associations were for male sex [prevalence odds ratio: 1.62 (95% confidence interval: 1.13-2.32)] and place of work outside of the city of Turin [prevalence odds ratio: 1.93 (95% confidence interval: 1.07-3.47)]; furthermore associations were relatively weak. An association was also found between nonresponse in survivors and nonresponse in their general practitioners [prevalence odds ratio: 3.40 (95% confidence interval: 2.54-4.56)]. In conclusion, apart from age, marital status and period of diagnosis, there were little differences between respondent and nonrespondents, for the considered clinical and demographical characteristics. Participation of survivors and their general practitioners correlated, suggesting that involvement of the general practitioners in the study may be a method to increase participation of survivors of childhood cancers.

Several studies report increasing trends in the incidence of childhood acute lymphoblastic leukemia (ALL). Because ALL may generate in utero, this study investigated if maternal age and birth cohort influence ALL temporal trends. Data on 252 ALL cases in children ages 1 to 5 years were extracted from the population-based Childhood Cancer Registry of Piedmont, Italy. Information on cases' maternal age and year of birth was obtained from the registry, whereas population data were obtained for children born in 1980 to 1997. Incidence rates were analyzed using an age-period-cohort approach, in which the period effect was represented by the child year of birth, the age effect by the maternal age at the time of delivery, and the cohort effect by the maternal birth cohort. ALL incidence increased over the study period [annual percentage change 2.49%; 95% confidence interval (95% CI), 0.09-4.93]. A linear effect of the maternal time variables (P = 0.012) was found, which was equally described by maternal age (direct association) and maternal birth cohort (inverse association). The annual percentage change was 1.83% (95% CI, −0.59-4.31), when maternal age was included in the model, and 5.72% (95% CI, 2.29-9.27), when maternal year of birth was included. In conclusion, maternal characteristics substantially affect temporal trends in childhood ALL incidence. (Cancer Epidemiol Biomarkers Prev 2007;16(2):347–51)

The aim of this study was to estimate how many deaths have been avoided because of the substantial improvement in childhood cancer survival both in Piedmont (2769 incident cases) and in Italy during 1970-1999. For each time period of diagnosis, the number of avoided deaths within 5 years after diagnosis was estimated as the difference between the observed number of deaths and the number of deaths that would have been observed if the patients had experienced the same mortality as in the reference period of 1970-1974. The national estimate of the number of avoided deaths was calculated by applying Piedmont cumulative mortality to the expected number of incident cases in Italy. An increase in the number of avoided deaths from 103 (95% confidence interval: 65-140) in 1975-1979 to 239 (95% confidence interval: 209-268) in 1995-1999 was observed in Piedmont. In Italy, the number of avoided deaths was 3880 in 1995-1999, with respect to 1970-1974. Results of these analyses provide an effective way to quantify the improvement in the quality of care for children with childhood cancer.

Background Prognosis for most types of childhood tumours has improved during the last few decades. In this article we estimate up-to-date period survival for less common, but important childhood malignancies in Europe. Methods Using the database of the Automated Childhood Cancer Information System we calculated period estimates of 10-year survival for the 1995–1999 period for children aged 0–14 years diagnosed during 1985–1999 with tumours of the sympathetic nervous system (NS), retinoblastoma, renal tumours, bone tumours and soft tissue sarcomas in four European regions. Results Ten-year period survival for 1995–1999 was 66% in children with tumours of the sympathetic NS, 96% for retinoblastoma, 87% for renal tumours, 58% for bone tumours and 61% for soft tissue sarcomas. The higher period estimates, as compared with cohort and complete estimates indicate recent improvement in survival for tumours of the sympathetic NS and to a lesser extent for retinoblastoma and renal tumours. Region-specific period survival estimates were lowest for Eastern Europe for renal, bone and soft tissue tumours, but not for the other two tumour groups. Conclusion There have been further improvements in the 1990s in long-term survival of children diagnosed with several malignancies, albeit to a different extent in different European regions.

Published data on time trends in the incidence of childhood leukaemia show inconsistent patterns, with some studies showing increases and others showing relatively stable incidence rates. Data on time trends in childhood cancer incidence from the Childhood Cancer Registry of Piedmont, Italy were analysed using two different approaches: standard Poisson regression and a Bayesian regression approach including an autoregressive component. Our focus was on acute lymphoblastic leukaemia (ALL), since this is hypothesised to have an infectious aetiology, but for purposes of comparison we also conducted similar analyses for selected other childhood cancer sites (acute non-lymphoblastic leukaemia (AnLL), central nervous system (CNS) tumours and neuroblastoma (NB)). The two models fitted the data equally well, but led to different interpretations of the time trends. The first produced ever-increasing rates, while the latter produced non-monotonic patterns, particularly for ALL, which showed evidence of a cyclical pattern. The Bayesian analysis produced findings that are consistent with the hypothesis of an infectious aetiology for ALL, but not for AnLL or for solid tumours (CNS and NB). Although sudden changes in time trends should be interpreted with caution, the results of the Bayesian approach are consistent with current knowledge of the natural history of childhood ALL, including a short latency time and the postulated infectious aetiology of the disease.

Several studies have been published on trends in childhood cancer incidence, with different patterns being reported. We present an analysis of cancer incidence trends in Piedmont (Italy) in 1967-2001 for the major categories of childhood malignant neoplasms.The population-based Childhood Cancer Registry of Piedmont has recorded incident cases of malignant neoplasm in children (age 0-14) since 1967. Procedures for data collection and coding have been uniform throughout the study period. We calculated incidence rates per million children per year by sex and age-group. Trends were estimated using Poisson regression analysis, adjusted for age and sex and presented as the annual percent change (APC).Significant increases were observed for all malignant neoplasms combined (3360 cases, APC:1.3%, 95% CI:1.0% to 1.6%), leukemia (APC: 1.0%, 95% CI: 0.4% to 1.6%), central nervous system (CNS) tumors (APC of 2.3%, 95% CI: 1.6% to 3.1%) and neuroblastoma (APC: 2.3%, 95% CI: 1.0% to 3.5%). Acute lymphoblastic leukemia (APC 1.2%, 95% CI: 0.2% to 2.3%), and Acute non-lymphoblastic leukemia (APC 1.7%, 95% CI-0.6%, 4.1) both increased over time. Differences by age groups were observed for some tumor types, such as for neuroblastoma in infants (4.8% increase per year), leukemia in children aged 1-4 years (1.2%) and CNS tumors in children aged 10-14 (3.4%).Our data suggest an increasing incidence of childhood cancer in general, and specifically for leukemia, CNS tumors and neuroblastoma in Piedmont in 1967-2001. The observed trends are unlikely to be explained by random variation, changes in exhaustiveness or quality of data collection and registration.

The aim of this report is to provide an update on the natural history of the Cri du Chat Syndrome by means of the Italian Register (I.R.). Two hundred twenty patients were diagnosed by standard cytogenetic methods and 112 of these were also characterised by molecular-cytogenetic investigation (FISH). FISH analysis showed interstitial deletions, short terminal deletions and other rare rearrangements not previously correctly diagnosed by standard cytogenetics. The diagnosis was made in the first month of life in 42% and within first year in 82% of cases. The remaining 18% were diagnosed at an age ranging from 13 months to 47 years. At the last follow-up, patient age ranged from 8 months to 61 years. Mortality, already low, has decreased over time as it is lower between 1984-2002 compared to 1965-1983. Mortality was higher in patients with unbalanced translocations resulting in 5p deletions. Our data confirm that the cat-like cry and peculiar timbre of voice are the most typical signs of the syndrome, not only at birth but also later and these are the only signs which might suggest the diagnosis in patients with small deletions and mild clinical picture. A cytogenetic and clinical variability must be underlined. Cardiac, cerebral, renal and gastrointestinal malformations were more frequent in the patients with unbalanced translocations resulting in 5p deletions. Sucking and feeding difficulties and respiratory infections are frequent in the first months or years of life. Intubation difficulties linked to larynx anomalies must be considered. Psychomotor development is delayed in all patients but there is a variability related to deletion size and type as well as other genetic and environmental factors. However, the results showed an improvement in the acquisition of the development skills and progress in social introduction which should encourage caregivers and parents to work together in carrying out the rehabilitative and educational interventions.