Adverse health outcomes and health concerns among survivors of various childhood cancers: Perspectives from mothers.

Advanced therapies have improved outcomes and also resulted in a growing risk of long-term adverse health events. This study intends to estimate incidences of adverse health events and examine differences in adverse health events among childhood cancer survivors, and to understand the concerns of mothers after their child has completed cancer treatment. An explanatory sequential mixed-method was used. A total of 201 paediatric cancer survivors' mothers with mean age 43.6 years were recruited. Of the survivors, 12.4% experienced five or more adverse health events. The incidence of adverse health events of altered body image, fatigue and neurocognitive problems were 31.54%, 14.77% and 12.53% respectively. Among survivors, significant differences in adverse health events of pain, endocrine problems and altered body image issues were identified. Survivors receiving radiotherapy, bone marrow transplants or completing treatment after 6-10 years experienced significantly more adverse health events. Maintaining health was the greatest concern for mothers, and the qualitative reports of their concerns could be categorised: living in uncertainty, and keeping forward-looking. Childhood brain tumour survivors were identified as experiencing more adverse health events than other survivors. The need for healthcare teams to consider mothers' health concerns was highlighted.

Effect of gadobutrol on VX2 magnetic resonance diffusion-weighted imaging.

The aim of this study was to evaluate the effect of contrast agent gadobutrol on the magnetic resonance diffusion-weighted imaging (MR DWI). Gadobutrol has higher relaxivity than Gd-DTPA and it also has higher formulation 1.0 M than Gd-DTPA 0.5 M. VX2 tumor implanted on the left thigh of each New Zealand rabbit was used as the animal model. The MR scanning was performed using a 1.5 T clinical whole-body MR scanner with an 8-channel knee coil. The results showed that there were significant differences in the signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) values between tumor and muscle both before and after gadobutrol injection (0.1 mmol/kg). However, there were no significant differences in the SNR and ADC values of tumor or muscle before and after gadobutol administration. There were also no significant difference in the contrast-to-noise ratio (CNR) values of tumor and muscle before and after gadobutrol injection.

Long-term results of Taiwan Pediatric Oncology Group studies 1997 and 2002 for childhood acute lymphoblastic leukemia.

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.

Nail changes associated with chemotherapy in children.

BACKGROUND: Large series of chemotherapy-induced nail changes in children have rarely been reported in the literature. OBJECTIVE: To study the pattern and onset of nail changes in cancer children receiving various chemotherapy regimens. METHODS: A cross-sectional study was performed on 30 paediatric patients (aged 1-17, mean 8.3 years), including 11 with acute lymphoblastic leukaemia, five with acute myeloid leukaemia, and others. RESULTS: Nail changes developed in 10 children during chemotherapy, five of whom had Muehrcke's lines, three Beau's lines, one Mees' lines and another had trachyonychia. There appeared to be no correlation between the pattern of nail alteration and the underlying cancer types or stages, or the regimens of chemotherapy. CONCLUSION: One third of the children with cancers developed nail changes associated with chemotherapy. Among them, Muehrcke's lines were the most common manifestation, which were unrelated to hypoalbuminaemia in our series.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

The Quantitative Assessment of Gd-DTPA in Contrast Enhanced Magnetic Resonance Angiography.

Recently, the use of MRI contrast agents has been proven to be substantially improved sensitivity and specificity in many clinical applications. CE-MRA has higher blood signal based on the T1 and T2-shortening property of contrast agents, so that even the small vessels can be visualized. The use of contrast agents can improve lesion detection and characterization. The routinely used dose of contrast agents in the routine MRI examinations only relies on the weight of the subject. The purpose of this study is to obtain the clinically optimal dose for 3D-TOF (time-of-flight) pulse sequences for CE-MRA examinations. In the phantom study, ten test tubes were filled with saline mixed with different dose of Gd-DTPA. It is found that the optimal dose of Gd-DTPA for saline phantom by using 3D-TOF pulse sequences is 20 mM. Also, there has no differences of optimal doses between Omniscan and Magnivist contrast agents Gd-DTPA. The results show that consistent high quality CE-MRA images might be obtained by using 0.25M Gd-DTPA (half of the routine dose) with 3~4 cc/sec injection rate for all clinical cases. The benefits of this study might be to minimize dose and potential toxicity. Additionally, the decrease of the cost of contrast agents might be achieved. It is expected to provide the recommended dose of Gd-DTPA for contrast enhanced MRA in clinical routine diagnosis.

Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis.

BACKGROUND: The long-term use of methamphetamine (MAMP) can result in psychosis but it is not clear why some individuals develop psychotic symptoms, while others use MAMP regularly over long periods and remain unscathed. We set out to characterize MAMP users and to examine the relationship of pre-morbid personality, pre-morbid social function and other psychiatric disorders to MAMP psychosis. METHOD: Four hundred and forty-five amphetamine users were recruited from a psychiatric hospital and a detention centre in Taipei, and were assessed with the Diagnostic Interview for Genetic Studies (DIGS). Their parents were interviewed with the Premorbid Schizoid and Schizotypal Traits (PSST) and the Premorbid Social Adjustment (PSA) schedules. Pre-morbid characteristics and psychiatric co-morbidity were compared between the MAMP users with a lifetime diagnosis of MAMP psychosis and those without. RESULTS: The MAMP users with psychosis presented a clinical picture which mimicked the positive symptoms of schizophrenia: 85% had auditory hallucinations; 71% persecutory delusions; 63% delusions of reference. Compared with their non-psychotic counterparts, these MAMP users were younger at first MAMP use, used larger amounts of MAMP, had a significantly higher mean PSST score, and higher rates of major depressive disorder, alcohol dependence and antisocial personality disorder. CONCLUSIONS: Earlier and larger use of MAMP was associated with increased risk of psychosis. Our data are also compatible with the view that pre-morbid schizoid/schizotypal personality predisposes MAMP users to develop psychosis, and that the greater the personality vulnerability, the longer the psychosis will persist.

Pedunculated malignant peripheral nerve-sheath tumour of the diaphragm presenting as recurrent lung infection: ultrasound diagnosis.

We report a rare case of malignant peripheral nerve-sheath tumour of the diaphragm in a 12-year-old boy with neurofibromatosis presented clinically and radiographically as recurrent lung infection. Ultrasound revealed a pedunculated diaphragmatic tumour invading the posterior chest wall. This case highlights that this unusual tumour may limit diaphragmatic excursion leading to, and even being masked by, superimposed lung infection. In patients with neurofibromatosis, ultrasound is recommended when chest radiography shows a basal lung opacity.

Evaluation for synergistic suppression of T cell responses to minor histocompatibility antigens by chloroquine in combination with tacrolimus and a rapamycin derivative, SDZ-RAD.

The 4-aminoquinolines, chloroquine and hydroxychloroquine, can suppress chronic graft-versus-host disease (GVHD) following blood and marrow transplantation (BMT) in mice and humans, respectively. We hypothesized that chloroquine in combination with tacrolimus and the rapamycin derivative SDZ-RAD can synergistically suppress T cell responses and antigen-presenting cell (APC) function in vitro. We used the APC-dependent C57BL/6 anti-BALB.B T cell response and APC-independent anti-CD3epsilon antibody-induced response to evaluate the role of synergism between chloroquine and tacrolimus or SDZ-RAD on each component of a T cell response to minor histocompatibility antigens. We found that chloroquine with tacrolimus had a greater synergistic suppression of APC-dependent compared to the APC-independent T cell responses, with a combination index (CIx) for 50% inhibition by mean effect analysis of 0.16 and 0.50, respectively (a lower number indicates greater suppression). By contrast, chloroquine with SDZ-RAD had a similar CIx between the two responsed 0.50 vs0.45) suggesting only T cell suppression. Synergy between chloroquine and SDZ-RAD involved a direct effect on T cell cytokine production, whereas synergism between chloroquine and tacrolimus was due to an effect on both T cells and APCs. We conclude that the renal-sparing 4-aminoquinolines may be used syneristically with immunosuppressive drugs currently used for BMT.

Probing enhanced cytochrome P450 2B1/2 activity in rat hepatocyte spheroids through confocal laser scanning microscopy.

Cytochrome P450 (CYP450) enzymes are essential for xenobiotic metabolism. Although CYP450s are found in many tissues, CYP2B1/2 are primarily expressed in the rat liver. The constitutive expression in vivo of CYP2B1/2 is low but it is induced in the presence of various drugs such as phenobarbital (PB). In this study, CYP2B1/2 activity in cultured hepatocytes was assessed in situ with the introduction of a fluorogenic substrate, pentoxyresorufin. The product of 7-pentoxyresorufin-O-dealkylation (PROD), which is catalyzed specifically by CYP2B1/2, was detected using confocal laser scanning microscopy (CLSM). Primary hepatocytes cultured as monolayers on collagen-coated surfaces exhibited background PROD activity and minimal PB inducibility after 4 days in culture. In contrast, rat hepatocytes organized in compacted aggregates, or spheroids, exhibited higher levels of PROD activity and retained their ability for PB induction. The results from the CLSM analysis were verified by RT-PCR and Western immunoblotting analysis. Furthermore, CLSM in conjunction with image processing techniques and three-dimensional reconstruction revealed the localization of enhanced PROD activity in the center of spheroids. The results support the use of CLSM as a powerful tool for investigating CYP2B1/2 activity in cultured rat hepatocytes.

Primary spinal epidural non-Hodgkin's lymphoma in a child.

Non-Hodgkin's lymphoma usually involves the central nervous system by metastatic disease. Primary spinal epidural non-Hodgkin's lymphoma (PSENL) is a relatively rare cause of spinal cord compression. It mainly occurs in adults past the 4th or 5th decades. This entity is even rarer in children. The proper treatment modalities are controversial in adults with PSENL. Radiotherapy is the main strategy after surgery; the role of chemotherapy is uncertain. Therapeutic experience in childhood PSENL is extremely limited. We report a 10-year-old boy presenting with backache and bilateral lower leg weakness after minor trauma. Small non-cleaved cell non-Hodgkin's lymphoma of the epidural space was proven after subtotal tumor removal. Other investigations including computed tomography of the chest and abdomen, bone scan, gallium scan, bone marrow aspiration, and cerebrospinal fluid study were all negative for occult disease. The patient received combined therapy with irradiation and chemotherapy after surgery. Esophageal stricture resulting from radiotherapy developed during treatment and colon interposition was performed. He has remained disease free 42 months after the diagnosis with normal functional status.

Treatment results of the TPOG-NHL92 protocols for childhood non-Hodgkin's lymphomas in Taiwan: a report from the Taiwan Pediatric Oncology Group (TPOG)

A nation-wide chemotherapeutic trial for childhood non-Hodgkin's lymphoma (NHL) was conducted by the Taiwan Pediatric Oncology Group (TPOG). Four TPOG-NHL92 protocols based on stage and histology were activated in 1992: TPOG-92LD (treatment duration: 8 months) was used for localized (stages I/II) NHL with any histology, 92LB (2 years), 92SNC (5 months), and 92LC (1 year) for advanced (stages III/IV) lymphoblastic (LB), small non-cleaved cell (SNC), and large cell (LC) lymphoma, respectively. From January 1992 through June 1998, 200 children with newly diagnosed NHL from 13 member hospitals of TPOG were enrolled. There were 140 boys and 60 girls. Their ages at diagnosis ranged from 2.4 months to 18.3 years with a median of 8.2 years. There were 54 (27.3%) patients with LB, 94 (47.5%) with SNC including B-cell acute lymphoblastic leukemia (B-ALL), and 50 (25.2%) with LC. Stages I, II, III, and IV (including B-ALL) of the disease comprised 5%, 10%, 43%, and 42% of cases, respectively. There were 176 patients eligible for evaluation of treatment results. The remission rate of induction was 82.4%, induction failed in 22 (12.5%) patients, and nine patients died during induction. As of August 31, 1999, 26 patients relapsed, six died during remission, one patient developed secondary acute myelomonocytic leukemia, and 105 patients remained in continuous remission with a median remission duration of 49 months. The event-free survival (EFS) at 7 years was 63.5%, 61.5% and 65% for LB, SNC, and LC groups (P = 0.8298). The 7-year EFS for stages I/II, III, and IV of the disease was 73%, 68.9%, and 50.3% (P = 0.0212), respectively. We concluded that following the strategy of stratification of therapy, only disease stages had prognostic significance in this study. More efforts are needed to improve our treatment results.

Epstein-Barr virus associated with immune thrombocytopenic purpura in childhood: a retrospective study.

OBJECTIVE: Although Epstein-Barr virus (EBV) is known to cause immune thrombocytopenic purpura (ITP), the epidemiology of this pathogen in children with ITP is not known. In the present study, the clinicoepidemiology and laboratory characteristics of EBV-associated ITP in childhood were analysed retrospectively. METHODS: The study cohort consisted of 108 children in whom ITP was diagnosed between 1990 and 1998. Patients were divided into EBV or non-EBV groups according to their serological status at diagnosis. RESULTS: Thirty-five (32.4%) of 108 children had ITP associated with acute EBV infection. The clinical manifestations and laboratory data were similar in children with and without acute EBV. Responses to various modalities of therapy were analysed. The average time to achieve complete remission (platelet count > or =150 x 10(9)/L) in EBV and non-EBV groups was 26 and 16 days, respectively. CONCLUSIONS: The incidence of childhood ITP associated with acute EBV infection is relatively high in Taiwan. Patients with EBV-associated ITP tended to resolve more slowly than those without EBV infection.

The annealing robust backpropagation (ARBP) learning algorithm.

Multilayer feedforward neural networks are often referred to as universal approximators. Nevertheless, if the used training data are corrupted by large noise, such as outliers, traditional backpropagation learning schemes may not always come up with acceptable performance. Even though various robust learning algorithms have been proposed in the literature, those approaches still suffer from the initialization problem. In those robust learning algorithms, the so-called M-estimator is employed. For the M-estimation type of learning algorithms, the loss function is used to play the role in discriminating against outliers from the majority by degrading the effects of those outliers in learning. However, the loss function used in those algorithms may not correctly discriminate against those outliers. In this paper, the annealing robust backpropagation learning algorithm (ARBP) that adopts the annealing concept into the robust learning algorithms is proposed to deal with the problem of modeling under the existence of outliers. The proposed algorithm has been employed in various examples. Those results all demonstrated the superiority over other robust learning algorithms independent of outliers. In the paper, not only is the annealing concept adopted into the robust learning algorithms but also the annealing schedule k/t was found experimentally to achieve the best performance among other annealing schedules, where k is a constant and is the epoch number.

Treatment of a transvestic fetishist with cognitive-behavioral therapy and supportive psychotherapy: case report.

Transvestic fetishism is a paraphilia marked by recurrent, intense sexually arousing fantasies, sexual urges, or behavior involving cross-dressing, in a heterosexual male. There are many explanations of the pathogenesis, but none are conclusive. Different treatments have been applied, but they generally remain obscure and disappointing. Transvestic fetishists rarely seek psychotherapy, because of their dynamic balance between perversion and intrapsychic disintegration. There are few studies, either qualitative or quantitative, associated with transvestic fetishism in Taiwan. This case report describes an adolescent transvestic fetishist who underwent a brief course of psychotherapy in the outpatient department of a psychiatric center in Taipei. After consultation for one year, he still maintained his deviant sexual behavior but also developed more severe moral anxiety. He was then referred for psychotherapy. Cognitive-behavioral and psychodynamic theories associated with transvestic fetishism were reviewed and applied in both understanding and treating this client. Some temporal effectiveness was achieved with combined cognitive-behavioral and dynamic-oriented supportive psychotherapy. After 18 sessions of psychotherapy over more than 4 months, the client was able to stop his perverse behavior and have fewer sexually arousing fantasies. The prognosis of transvestic fetishism is generally supposed to be pessimistic and have a high rate of recurrence. Some propose that adolescents have a better outcome after treatment. This case report reveals the possibility of change for a transvestic fetishist. However, the long-term effects of the brief course of psychotherapy require further evaluation in the future.

Receding cytochrome P450 activity in disassembling hepatocyte spheroids.

Primary rat hepatocytes can self-assemble to form multicellular spheroids when plated onto Primaria petri dishes or suspended in stirred vessels. These spheroids exhibit prolonged viability, enhanced liver-specific functions and differentiated ultrastructure compared to monolayer cultures. Upon transfer to collagen coated surface, or upon the addition of fetal bovine serum (FBS) to the culture, these spheroids began to disassemble and spread on the surface. The dynamics of cytochrome P450 CYP1A1/2 activity in the course of spheroid disassembly was examined in situ by detection of the fluorescent product, resorufin, of ethoxyresorufin O-dealkylation. Optical sectioning of the disassembling spheroids by confocal microscopy demonstrated that hepatocytes that reverted to monolayer exhibited markedly lower CYP1A1/2 activity than those that remained in a multilayered structure. This occurred whether the disassembly was caused by incubation with FBS-containing medium or by cultivation on a collagen-coated surface. When spheroids were cultured on the surface of agar, the disassembly process was retarded even in the presence of FBS. However, even in those intact spheroids, the exposure to FBS markedly decreased CYP1A1/2 activity. The decreased CYP1A1/2 activity was correlated to a diminished smooth endoplasmic reticulum as seen in the transmission electron micrograph. The results clearly demonstrate that the disassembly of hepatocyte spheroids led to decreased CYP1A1/2 activity. Furthermore, FBS contained a factor that caused CYP1A1/2 to decrease even in intact spheroids.

Inflammatory pseudotumor of the liver in Kostmann's disease.

A case in which inflammatory pseudotumor of the liver (IPTL) seemed to complicate severe congenital neutropenia (Kostmann's disease) is reported. IPTL is a rare entity, especially in childhood. The exact etiology of this lesion is unknown, but it is generally regarded as a benign, reactive inflammatory condition. Based on 15 reported pediatric cases in the literature, the causes, diagnosis, and treatment of IPTL are discussed.

Idiopathic thrombocytopenic purpura preceding malignant lymphoma: report of one case.

Idiopathic thrombocytopenic purpura (ITP) preceding malignant lymphoma is a rare condition. Most cases occur simultaneously with lymphoma or after it has been diagnosed. The case of a child with idiopathic thrombocytopenic purpura recovered after prednisolone treatment, but lymphoma developed four months later. The pathogenesis for idiopathic thrombocytopenic purpura evolving into malignant lymphoma is still unknown and further study is necessary.

Spleen rupture in infectious mononucleosis: report of one case.

Spleen rupture has been a rare but feared complication in patients with infectious mononucleosis. There have been many cases reported during the last decade. However, it has rarely been mentioned among the young infant group. Here, we present a case of an infant, two months of age, who suffered from spleen rupture due to infectious mononucleosis, and was latter cured by himself under conservative treatment.