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.

Transcription factor SPZ1 promotes TWIST-mediated epithelial-mesenchymal transition and oncogenesis in human liver cancer.

The epithelial-mesenchymal transition (EMT) is an important process in the progression of cancer. However, its occurrence and mechanism of regulation are not fully understood. We propose a regulatory pathway in which spermatogenic leucine zipper 1 (SPZ1) promotes EMT through its transactivating ability in increasing TWIST1 expression. We compared the expression of SPZ1 and TWIST1 in specimens of hepatocarcinoma cells (HCCs) and non-HCCs. Expression of SPZ1 exhibited a tumor-specific expression pattern and a high correlation with patients' survival time, tumor size, tumor number and progression stage. Moreover, forced expression and knockdown of SPZ1 in hepatoma cells showed that SPZ1 was able to regulate the cellular proliferation, invasion, and tumorigenic activity in a TWIST1-dependent manner in vitro and in vivo. These data demonstrate that SPZ1, a newly dscribed molecule, transactivates TWIST1 promoters, and that this SPZ1-TWIST axis mediates EMT signaling and exerts significant regulatory effects on tumor oncogenesis.

Risk factors influencing the outcome of peptic ulcer bleeding in end stage renal diseases after initial endoscopic haemostasis.

Background and Aims: Patients suffering from peptic ulcer (PU) bleeding who have end-stage renal disease (ESRD) may encounter more adverse outcomes. The primary objective is to investigate the risk factors that influence the outcomes of ESRD and chronic kidney disease (CKD) patients with PU bleeding after successful initial endoscopic haemostasis. Methods: A total of 540 patients with PU bleeding after initial endoscopic haemostasis in a tertiary hospital were investigated retrospectively. They were sorted into three groups after randomised age-matched adjustment: ESRD group (n = 90), CKD group (n = 90) and control group (n = 360). Main outcome measurements were rebleeding, requirement for blood transfusion and surgery, length of hospital stay and mortality. Results: The rebleeding rates were 43% for the ESRD group vs. 21% for the CKD group vs. 12% for the control group (overall p = < 0.001). Multivariate analysis showed the predictors of rebleeding were ESRD, time to endoscope, and non-high-dose proton-pump inhibitors (PPI) users. The risk factors for bleeding-related mortality were presence of moderate degree of CKD and ESRD group, time to endoscope, and Rockall score. All-cause mortality was related to presence of moderate degree of CKD and ESRD group, platelet count, time to endoscope, Rockall score and length of hospital stay. Conclusions: ESRD patients who suffered from PU bleeding were at risk of excessive rebleeding and mortality with frequent occurrence of delayed rebleeding. This study suggests that early endoscopy for initial haemostasis and high-dose intravenous PPI are associated with the reduction of rebleeding risk especially in patients with high Rockall scores.

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.

Sonographic patterns of splenic abscess: an analysis of 34 proven cases.

BACKGROUND: The sonographic patterns of splenic abscess are seldom reported. We report the different sonographic patterns in 34 proven cases. METHODS: From 1984 to June 2000, 42 patients were diagnosed with splenic abscess by abscess aspiration or pathologic findings of surgical specimens. Among them, 34 cases underwent sonographic studies. RESULTS: Fifteen cases had typical abscess echo patterns that included gas in the abscess (two cases) and debris in the abscess cavity (13 cases). Five cases of abscess showed subcapsular lesions with or without echo in the lesion. Two cases of abscess showed a thickened wall mimicking a tumor with central necrosis. Two cases showed a pattern suggesting a cyst. Ten cases showed a pattern suggesting tumor: eight had multiple lesions and two had solitary lesions. Of those 10 cases, seven multifocal abscesses were hypoechoic, and two solitary and one multifocal abscess were mixed echoic. Mortality from multiple splenic abscesses was higher than that from solitary abscess (p = 0.032). Both patients with gas in the abscess expired. CONCLUSION: Sonography of a splenic abscess is variable. A typical pattern was seen in only 44.1% (15 of 34) of patients in our series. We suggest using needle aspiration in each suspected case. Multiple and gas-containing abscesses indicate a poor prognosis.

Mutations in the NS3 gene and 3'-NCR of Japanese encephalitis virus isolated from an unconventional ecosystem and implications for natural attenuation of the virus.

The T1P1 strain of Japanese encephalitis (JE) virus was recently isolated from paddy-free Liu-Chiu Islet in which natural JE antibody has been prevalent. In mouse neuroblastoma-derived Neuro-2a cells, T1P1 appeared significantly lower in virus productivity than another local isolate, CH1392. It implied that this new isolate possesses a characteristic viral replication pattern other than that of CH1392. T1P1 has also shown lower neurovirulence, which was reflected by a significantly higher LD(50) (2.44 x 10(6) PFU) than CH1392 (2.87 x 10(2) PFU). In comparison of the full-length RNA sequences between T1P1 and CH1392, a total of 7 nucleotides, including 1 in preM/M and 2 each in NS3, NS5, and the 3'-end noncoding region (NCR), appeared different. Of them, only the changes in NS3 (position 325, T for CH1392, A for T1P1; and position 364, G for CH1392 and A for T1P1) resulted in substitutions of deduced amino acids. There were two additional nucleotide changes appearing in the 3'-NCR. The amino acids 109 Phe and 122 Glu in NS3 of CH1392 were substituted by Ile and Lys, respectively, in T1P1. The unique growth properties and low virulence of T1P1 presented in this report were likely related to abnormal enzymatic activity due to mutations of the NS3 gene (especially position 364) and possibly to the mutations in the 3'-NCR. The natural attenuation of T1P1 that has been circulating in paddy-free Liu-Chiu Islet may account for the absence of clinical JE cases in past years.

Acute lymphoblastic leukemia in one of two siblings with Alstrom syndrome.

Alstrom syndrome is a rare autosomal recessive disease; less than 60 cases have been reported. No Chinese patient with this disease has been reported previously in the literature. Here, we describe an 11-year-old Chinese boy with this condition. His elder sister also had Alstrom syndrome, and his father had non-insulin-dependent diabetes mellitus. Both siblings had degenerative retinopathy, obesity, mental retardation, perceptive hearing loss, short stature, non-insulin-dependent diabetes mellitus, nephropathy, hyperlipidemia, acanthosis nigricans, and hepatic dysfunction. The boy also developed acute lymphoblastic leukemia, which was confirmed by cytochemistry and immunophenotyping findings. He received chemotherapy and radiotherapy for the malignancy. The present case suggests that acute lymphoblastic leukemia may be coincident with or may be a previously undescribed systemic manifestation of Alstrom syndrome.

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.

Tc99m sulfur colloid scintigraphy for detection of intrathoracic extramedullary hematopoiesis in patient with beta-thalassemia major--a case report.

Extramedullary hematopoiesis (EMH) refers to the production of blood cells outside the bone marrow and is a compensatory mechanism for bone marrow dysfunction. A 34 year-old female patient with beta thalassemia major was found to have multiple large, well-circumscribed radiopaque paravertibral mass lesions in chest radiography. Magnetic resonance imaging (MRI) of the thorax disclosed a right upper apical and two lower thoracic paraspinal mass lesions with heterogeneous isointensity on T1-weighted images and hypointensity on T2-weighted images. Because intrathoracic EMH is suspected in our case, which had obvious bone marrow dysfunction, radionuclide bone marrow scintigraphy is helpful in supporting the diagnosis. Tc99m sulfur colloid scintigraphy demonstrated three intense radioactive thoracic paraspinal mass lesions corresponding to the lesions seen on MRI. We believe whole body bone marrow scintigraphy with Tc99m sulfur colloid is the best convenient noninvasive method for supporting the diagnosis of EMH.

Thrombocytosis in children at one medical center of southern Taiwan.

Thrombocytosis in children is common, but usually without symptoms. The causes of thrombocytosis in children are considered to be mostly due to infection, trauma, surgery, blood disease, prematurity, renal disease and chronic inflammation. To evaluate the incidence and etiology of thrombocytosis of the hospitalized patients, patients who were admitted to the Pediatric Department of Kaohsiung Medical College Hospital (KMCH) from October 1996 to November 1997 were studied. There were 2910 cases studied and 220 cases (127 male and 93 female) had thrombocytosis (> or = 500 x 10(9)/L) with a rate of 7.6%. The causes of thrombocytosis are infections (49.5%), Kawasaki disease (6.4%), postsplenectomy (7.8%), blood diseases (3.7%), malignancies (3.2%), renal disorders (3.2%), prematurity (3.2%), tissue damage (4.5%), chronic inflammation (1.8%), recovery from marrow suppression (1.3%), immunologic disturbances (2.2%), essential thrombocythemia (0.5%), and miscellaneous factors (3.7%). Thrombocytosis associated with multiple, simultaneous causative factors was found in 9.0% of these cases. Thrombocytosis secondary to infectious diseases or Kawasaki disease was significantly more common in children under 2 years old. The most commonly associated infectious disease was respiratory tract infection (61.1%). There were 29 children (13.2%) presenting a platelet count of more than 800,000/mm3. However, no thrombotic complications were seen in any of the children. By far, the major cause of thrombocytosis in our cases was reactive in character. Most of the thrombocytosis cases were due to infections, inflammatory diseases, or Kawasaki disease.

Endoscopic injection sclerotherapy with 1.5% Sotradecol for bleeding cardiac varices.

The authors retrospectively studied the efficacy of endoscopic injection sclerotherapy (EIS) with 1.5% Sotradecol (STD) in patients with bleeding cardiac varices (CV). Case histories of 27 patients with large, isolated, bleeding CVs were reviewed. Case records of another 27 patients with isolated esophageal varices (EV), matched for age, sex, and year EIS was performed, were selected from a computer data bank as controls. Using a small volume (2-4 ml) of injection per vessel, the rate of immediate control of bleeding was 66.7% (18 of 27) in the CV group and 70.4% (19 of 27) in the EV group. The early rebleeding rate was higher for patients in the EV group (48.1%, 13 of 27) than for those in the CV group (18.5%, 5 of 27) (p = 0.0209). On the other hand, it was more difficult to control the rebleeding from CV (p = 0.00494). In terms of mortality, there was no statistically significant difference between the CV and EV groups (33.3 versus 29.6%) within 1 week after EIS, but the 1-month post-EIS mortality rate was significantly higher (p = 0.0278) in the CV group (18 of 27, 66.7%) than in the EV group (10 of 27, 37.0%). Among those in the CV group who died of late complications within 1 month after EIS, three died of recurrent hemorrhage, five of infection, and one of viscus perforation. In the EV group, only two patients died of infection. Thus, it was concluded that EIS with small volumes (2-4 ml) of 1.5% STD was equally effective in controlling immediate bleeding from CV and EV. However, it was more difficult to control early rebleeding from CV, and the mortality and complications within 1 month after EIS were significantly higher in patients with CV. These observations are currently under careful study and evaluation.

RS-66271, a C-terminally substituted analog of human parathyroid hormone-related protein (1-34), increases trabecular and cortical bone in ovariectomized, osteopenic rats.

It was predicted from the amino acid sequence of the bone anabolic peptides, parathyroid hormone (PTH) (1-34) and PTH related protein (PTHrP) (1-34), that the C-terminal amino acids form an amphipathic alpha-helix. Therefore, we substituted a model amphipathic alpha-helical peptide (MAP) sequence in the C-terminal region of hPTHrP(1-34), obtaining RS-66271 ([MAP1-10]22-31 hPTHrP(1-34)-NH2). The anabolic activities of RS-66271 and hPTHrP(1-34) were evaluated in 3-month-old, ovariectomized (OVX) osteopenic rats. Subcutaneous injection of hPTHrP(1-34) at 80 micrograms/kg/day partially reversed estrogen depletion trabecular bone loss but was ineffective in the cortex. In contrast, RS-66271 dose-relatedly reversed loss at both sites and, at 80 micrograms/kg/day, returned both trabecular and cortical bone calcium to the level of sham-operated controls. Histomorphometric analysis showed significantly elevated bone formation rates over vehicle-treated OVX in both trabecular and cortical tibial bone following treatment with RS-66271. Electron microscopy showed an increase in the relative surface area of vertebral trabeculae covered by osteoblasts in animals treated with RS-66271. These studies demonstrate that the C-terminal amino acids of hPTHrP(1-34) can be replaced by a model amphipathic helix and that the new chemical entity has greater anabolic activity than the parent peptide. The results suggest that RS-66271 may be a candidate molecule for the treatment of human osteoporosis.

[Small cell lung cancer with liver and bone metastasis associated with hypercalcemia and acute pancreatitis--a case report].

A 67-year-old man was hospitalized with the chief complaint of diffuse abdominal pain for 3 days. Hypercalcemia and acute pancreatitis was found by laboratory examination. Abdominal CT scans showed swelling of the pancreas, multiple liver tumors and osteolytic lesions of bone. Upper mediastinal lobulated mass was suspected from chest x-ray examination, then small cell lung cancer (SCLC) was proved by bronchoscopic and pathological examination. The final diagnosis is SCLC with liver and bone metastasis associated with hypercalcemia and acute pancreatitis. After pancreatitis subsided, the patient was put on chemotherapy. Unfortunately, due to immunocompromise, he died of pneumonia and sepsis. There was no reasonable explanation regarding to the cause of acute pancreatitis except hypercalcemia, which might be due to SCLC with bone metastasis. This is the first report of such a complication in a patient with SCLC.

Hydronephrosis accidentally detected by gastrointestinal sonography.

A retrospective study was carried out on patients with gastrointestinal complaints, who were accidentally found to have varying degrees of hydronephrosis between October 1989 and April 1991. The criteria for hydronephrosis given by Ellenbogen et al were used for ultrasonographic diagnosis. Grade 0 and 1 were classified as mild degree and grade 2 and 3 as moderate and severe, respectively. The causes of hydronephrosis were determined by intravenous pyelography, retrograde pyelography, and/or computed tomography. Of 44 patients with hydronephrosis who had complete studies, 20 had a mild degree of hydronephrosis, 18 had a moderate degree, and 6 had a severe degree. All 24 patients with moderate and severe degrees of hydronephrosis had obstruction as the etiology, but only 50% of the cases with mild hydronephrosis were found to have pathological lesions. Urolithiasis (79.4%) was the most common cause of hydronephrosis in this study. Benign prostate hypertrophy, carcinomas, external compression, and tuberculosis followed. Hydronephrosis found accidentally by sonography in the patients with gastrointestinal complaints is significant.

Prenatal and molecular diagnosis of beta-thalassemia major in Taiwan by naturally and amplified created restriction sites.

To characterize mutations rapidly in 43 patients with beta-thalassemia major in Taiwan, we utilized a method of natural and amplified created restriction site (ACRS) analysis for detection of beta-globin gene mutation. After analysis, eight different point mutations were found among 86 known chromosomes. IVS-2 nt 654 (C-->T), accounting for 40 of the 86 mutations with mutant beta-globin genes, is the most common mutation, followed by frameshift codons 41/42 (-TCTT) in 28 mutations, -28 mutation (A-->G) in 7 mutations, nonsense codon 17 (A-->T) in 5 mutations, frameshift codons 27/28 (insertion of C) in 2 mutations, IVS-1 nt 1 (G-->T) in 2 mutations, frameshift codons 71/72 (insertion of A) in 1 mutation, and IVS-1 3' end TAG-->GAG in 1 mutation. The first four mutations account for 80 of all 86 mutations of beta-thalassemia major in Taiwan. Furthermore, the beta-globin gene mutation was identified successfully in one chorionic villi biopsy for prenatal diagnosis and in specimen of blood from one patient who had received bone marrow transplantation (BMT). Complete diagnosis is possible in all of the Chinese families with beta-thalassemia in Taiwan, and the first trimester prenatal diagnosis can be achieved simply by using only 13 oligonucleotide primers and 10 restriction endonucleases. This non-radioactive assay was shown to be a rapid, sensitive, precise and safe method in detecting the mutations of beta-thalassemia in Taiwan.

Sequential invasions of pancreatic pseudocysts in pancreatic tail, hepatic left lobe, caudate lobe, and spleen.

A 66-year-old male patient without a history of risk factors for pancreatitis suffered from pancreatitis and developed pseudocyst. During the course of treatment and follow-up, the pseudocyst was found to have migrated through the pancreatic tail, left hepatic lobe, caudate lobe, and spleen on abdominal sonography and computed tomography scan. Finally, emergent laparotomy was done for splenic abscess and removal of infected pseudocyst in the spleen and lesser sac of the abdomen. The patient made a full recovery after operation.

Various sonographic patterns of smooth muscle tumors of the gastrointestinal tract: a comparison with computed tomography.

To evaluate the sonographic patterns of smooth muscle tumors of the gastrointestinal tract, we analyzed 25 patients with histologically confirmed smooth muscle tumors. Sonography revealed no abdominal mass in seven patients (sonogram-negative), and abdominal masses in 18 patients (sonogram-positive). The mean size of tumors in the sonogram-negative group (4.5 +/- 1.5 cm) was smaller than that in the sonogram-positive group (11.4 +/- 3.5 cm). We classified the various sonograms into three patterns. Comparing the sonograms with the computed tomographic pictures of each pattern, we theorized that the different patterns on sonograms may be caused by tumor necroses of different sizes with or without gas in the necrotic cavity. For the necrotic tumors, the size of the necrotic area did not correspond to the size of the tumor. However, the tumors with necroses were significantly larger than those without necroses. A central necrosis was found in cases exhibiting both leiomyosarcoma and leiomyoma. On comparing the sonogram-positive and sonogram-negative groups, we found that the size and location of a tumor may affect the detection rate of that tumor by sonography.

Liver biochemical tests and dengue fever.

The impact of dengue on liver function was studied by biochemical tests on 125 male and 145 female patients diagnosed with this disease during an outbreak that extended from November 1987 to December 1988. Abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase (G-GT) were observed in 93.3%, 82.2%, 7.2%, 16.3% and 83.0% of the patients, respectively. The elevation of transaminases was mild to moderate in most cases, but was 10-fold greater than the normal upper limit for AST and ALT in 11.1% and 7.4% of the patients, respectively. Initially, the level of AST was greater than that of ALT, increasing to maximum levels nine days after the onset of symptoms, then decreasing to normal levels within two weeks. Results of the biochemical tests did not differ significantly between the cases with and without hepatitis B or hepatitis C virus infection, but significantly higher elevations of AST, ALT, and G-GT were observed in patients with episodes of bleeding. Liver biopsies of two patients showed features of lobular hepatitis. Of the five fatal cases, three died of hepatic failure. It is concluded that dengue fever may cause hepatic injury and transaminase elevation similar to that in patients with conventional viral hepatitis. In epidemic or endemic areas, dengue fever infection should be considered in the differential diagnosis of hepatitis.

Sonographic detection of stones in poorly opacified left intrahepatic ducts.

Intrahepatic duct (IHD) stone is a common disease in Taiwan. In some cases, left IHD stones cannot be demonstrated by endoscopic retrograde cholangiography (ERC) or even by percutaneous cholangiography (PTC). This study was designed to evaluate the efficacy of sonography in demonstrating left IHD stones in poorly opacified left IHD by either ERC or PTC. Of 109 patients with hyperechoic nodular lesions in either the dilated left IHD or atrophic left lobe of the liver, with or without acoustic shadows, 49 patients were excluded because they refused further study. Among the remainder (60 patients), 33 patients had good opacification of left IHD in ERC or PTC. Stones were seen in 31 patients, and tumor obstruction in 2 patients. Twenty-seven patients had complete or partial absence of the left IHD in cholangiograms. Stones were found at surgery in 23 patients and by CT scan in 3 patients. Mucin-producing cholangiocarcinoma was found in 1 patient. The positive predictive value of the demonstration of stones in left IHD by ultrasound was 95% (57/60). Only 15% of patients with atrophy of the left hepatic lobe and stones were demonstrated by sonogram in this series. We conclude that the detection of left IHD stones by ultrasound in patients with poor opacification of the left IHD in cholangiograms is reliable procedure.