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Background: The importance of information technology to current business practices has long drawn the attention of practitioners and academicians. Aim: This paper aims to broaden understanding about service innovation as a critical organizational capability through which information technology adoption influences the competitive advantage of a firm. In the context of financial firms, this study examines how information technology is adopted and managed to enhance service innovation practices and whether and how service innovation practices may influence the competitive advantage of firms. Method: A research framework and the associated hypotheses are proposed. An empirical survey was conducted and questionnaires were mailed to 558 financial firms in Taiwan. Analysis: A total of 124 valid observations was collected and analysed using the partial least squares technique. Conclusions: The results suggest that adopting information technology has positive effects on service innovation practices, which increase the competitive advantage of firms.

Summary: Background: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. Objectives: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. Methods: We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. Results: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild‐type (triple‐WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2,BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC2,BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival. Conclusions: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes.Acral melanoma is the most common subtype of melanoma in Asians.KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment.Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival.These observations should be explored further for future drug development. Linked Comment: Johansson. Br J Dermatol 2020; 182:1085. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: International guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer. Methods: This retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size. Results: Some 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X‐ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively. Conclusion: This study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected. [ABSTRACT FROM AUTHOR]

The article details a study which investigated the clinical presentations and frequency of hereditary non-polyposis colorectal cancer in Taiwan through the use of the Amsterdam II (AC-II) criteria and immunohistochemistry (IHC). Using AC-II, the authors screened 7108 patients with primary colorectal cancer registered in Chang Gung Memorial Hospital's Colorectal Cancer Registry. IHC was used to analysed the mismatch repair genes of the tumour specimens.

Summary: Melanoma is a life‐threatening type of skin cancer. It affected about 351,800 people worldwide in 2015. Acral melanoma occurs on non‐hairy acral skin (palms, soles, and nail beds) and is not thought to be linked to ultraviolet radiation (e.g. from the sun), unlike other melanoma types (non‐acral melanoma). This study, conducted by researchers based in Taiwan, aimed to find out which mutations (abnormalities) in certain genes underly acral melanoma and non‐acral melanoma in Asians. This is known as 'genomic profiling', and allows scientists to find out about the genetic information related to a person or cell type and the way genes interact with each other. This profiling can be done using a type of genetic testing called next‐generation sequencing. The authors performed comprehensive genomic profiling of 409 cancer‐associated genes in 66 melanomas, comprised of 45 acral melanomas and 21 non‐acral melanomas. The authors found that the non‐acral melanomas showed a significantly higher frequency of a type of mutation called BRAF mutations than the acral melanomas. Meanwhile, the frequencies of other alterations (NRAS/KRAS mutations, cell cycle aberrations, anti‐apoptosis pathway alterations, and receptor tyrosine kinase gene gains) were significantly higher in the acral melanomas. Ulceration, in which the skin on the surface of the melanoma breaks down, was found at significantly higher rates in the acral melanomas and non‐acral melanomas with cell cycle aberrations and receptor tyrosine kinase gene gains. Notably, cell cycle aberrations and anti‐apoptosis pathway alterations were associated with a lower rate of survival in all 66 melanoma patients, and especially in the 45 acral melanoma patients. This study strengthens our understanding of the patterns and repercussions of gene mutations in acral and non‐acral melanoma in Asians. The study revealed that, in addition to treatments called immunotherapies, acral melanoma patients might benefit from treatments that target NRAS/KRAS mutations, cell cycle aberrations, receptor tyrosine kinase gains, and anti‐apoptosis pathways, a possibility which warrants study in the future. This is a summary of the study: Genetic alterations in primary melanoma in Taiwan. Linked Article: Sheen et al. Br J Dermatol 2020; 182:1205–1213 [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown., Patients and Methods: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR)., Results: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS., Conclusions: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status., Clinical Trials Number: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Considerable evidence suggests that aspirin has a chemopreventive effect on colorectal cancer (CRC). However, optimal dose and treatment duration have not been defined, and data on the effects of low-dose aspirin are contradictory., Aim: To determine if the incidence of CRC in patients with low-dose aspirin use was lower than in those without aspirin use., Method: From Taiwan's National Health Insurance research database, aspirin users (n = 1985) were defined as adults (age ≥20 years) with at least 3.5 years of regular low-dose aspirin use (50-150 mg per day) between 1998 and 2002. Non-users (n = 7940) were those who did not use aspirin and were matched 4:1 with the user group by age, gender, date of ambulatory care (index date), and presence of known risk factors for cardiovascular disease (including hypertension, diabetes mellitus and hyperlipidaemia). Follow-up of the two study groups was made until the end of 2010, and incidences and hazard ratios of colorectal cancer were determined., Results: During a median follow-up period of 8.9 years, 129 non-users and 14 users developed CRC, corresponding to incidence rates of 180.43 and 79.42 per 100,000 person-years respectively. Duration of aspirin use among users ranged from 3.5 to 12.6 years (mean 8.7 years). The multivariate-adjusted hazard ratio for CRC was 0.5 (95% confidence interval 0.28-0.87) among users as compared with non-users., Conclusions: Long-term use of low-dose aspirin appears to be associated with a lower incidence of CRC in patients with high cardiovascular risk. Further randomised clinical trials are necessary to confirm these findings., (© 2013 John Wiley & Sons Ltd.)

Aim: Pyogenic liver abscess (PLA) has been reported as an early manifestation of colorectal cancer (CRC) in adults, but few studies have investigated this relationship. It is unclear if patients with Klebsiella pneumoniae PLA are at increased risk of subsequent CRC. Our aims were to estimate the incidence of CRC among patients with PLA and to compare the incidence of CRC between K. pneumoniae PLA and non-K. pneumoniae PLA groups., Method: We conducted a retrospective study of patients with PLA diagnosed between 2000 and 2009 at a medical centre in northern Taiwan. CRC status and survival status were determined until December 2010. Incidence data from the general population were retrieved from the Taiwan Cancer Registry. Outcome measures were defined as standardized incidence ratio and the incidence rate per 100,000 person-years., Results: This study included 2294 patients, of whom 1194 (52%) had K. pneumoniae infection. During the follow-up period, 54 (2.3%) patients were diagnosed with CRC, corresponding to an overall incidence rate of 669.1 (95% CI, 490.7-847.6) per 100,000 person-years. The adjusted hazard ratio of CRC was 2.68 times greater for patients with K. pneumoniae PLA than for those with non-K. pneumoniae PLA (95% CI, 1.40-5.11)., Conclusion: Patients with K. pneumoniae PLA had a significantly higher rate of subsequent CRC than did patients with non-K. pneumoniae PLA. Colonoscopy is recommended to detect occult colonic malignancy in patients with PLA, particularly for patients over 60 years of age and with K. pneumoniae., (© 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.)

Familial adenomatous polyposis (FAP) is an autosomal-dominant disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. The affected individuals develop colorectal polyposis and show various extra-colonic manifestations. In this study, we aimed to investigate the genetic and clinical characteristics of FAP in Taiwanese families and analyze the genotype-phenotype correlations. Blood samples were obtained from 66 FAP patients registered in the hereditary colorectal cancer database. Then, germline mutations in the APC genes of these 66 polyposis patients from 47 unrelated FAP families were analyzed. The germline-mutation-negative cases were analyzed by performing multiplex ligation-dependent probe amplification (MLPA) and single-strand conformation polymorphism (SSCP) analysis of the MUTYH gene. Among the analyzed families, 79% (37/47) of the families showed 28 APC mutations, including 19 frameshift mutations, 4 nonsense mutations, 3 genomic deletion mutations, 1 missense mutation, and 1 splice-site mutation. In addition, we identified 15 novel mutations in 32% (15/47) of the families. The cases in which APC mutations were not identified showed significantly lower incidence of profuse polyposis (P = 0.034) and gastroduodenal polyps (P = 0.027). Furthermore, FAP families in which some affected individuals had less than 100 polyps showed significant association with low incidence of APC germline mutations (P = 0.002). We have added the APC germline-mutation data for Taiwanese FAP patients and indicated the presence of an FAP subgroup comprising affected individuals with nonadenomatous polyps or less than 100 adenomatous polyps; this form of FAP is less frequently caused by germline mutations of the APC gene.

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.

Aims: Protamine, when administered to neutralize heparin in cardiovascular surgery, is associated with occasionally severe antigen-antibody reactions associated with substantial morbidity and mortality. The objective of this study is to investigate whether patients on hemodialysis are more susceptible to the protamine adverse effects., Method: First, a retrospective analysis of a protamine-associated hypotension episode (PAHE) in 239 patients undergoing coronary artery bypass grafting surgery was performed for the incidence study in the period of 1999 to 2005. Second, an ELISA determination of serum anti-protamine IgG antibody in 255 serum samples from individuals without previous surgical histories was conducted for prevalence survey. In both studies, patients on HD were matched for age with non HD patients., Results: The highest incidence (57%) of PAHE occurred in patients on hemodialysis using of M-insulin (a mixed type of insulin aspart 30%, insulin aspart protamine 70%) formulation, and this group also exhibited a high anti-protamine IgG antibody titer in serum (odds ratio: 18.31)., Conclusions: A substantial proportion of patients on hemodialysis are at high risk of acquiring protamine adverse effects, but definite conclusion about the association between uremia and PAHE, however, still needs to be made with caution.

Background: Quality of end-of-life care received by cancer patients has never been explored in an entire Asian country for all ages and cancer groups., Patients and Methods: Retrospective cohort study to examine trends in quality of end-of-life care among a cohort of 242 530 Taiwanese cancer patients who died in 2000-2006., Results: In the last month of life, cancer care tended to become increasingly aggressive as shown by (i) intensive use of chemotherapy (15.45%-17.28%), (ii) frequent emergency room visits (15.69%-20.99%) and >14-day hospital stays (41.48%-46.20%), (iii) admissions to intensive care units (10.04%-12.41%), and (iv) hospital deaths (59.11%-65.40%). Use of cardiopulmonary resuscitation (13.09%-8.41%), intubation (26.01%-21.07%), and mechanical ventilation (27.46%-27.05%) decreased, whereas use of hospice services increased considerably (7.34%-16.83%). Among those receiving hospice services, rates of referrals to hospice services in the last 3 days of life decreased from 17.88% to 17.13% but remained steady after adjusting for selected covariates., Conclusions: The quality of end-of-life care for Taiwanese cancer decedents was substantially inferior to that previously reported and to that recommended as benchmarks for not providing overly aggressive care near the end of life.

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.

Background: We determined the maximum tolerated dose (MTD) and then further evaluated the response rate and safety profile of gemcitabine (Gem) plus doxorubicin (Dox) in chemonaïve patients with advanced hepatocellular carcinoma (HCC)., Patients and Methods: Dose escalation was tested over four dose levels in each 21-day cycle: level 1 (Gem 1000 mg/m(2) on days 1 and 8, Dox 30 mg/m(2) on day 1), level 2 (Gem/Dox 1250/30), level 3 (Gem/Dox 1250/45) and level 4 (Gem/Dox 1250/60). The MTD was further evaluated in phase II., Results: Patients' characteristics were: 47 men, three women; median age 53 years (range 28-70); Zubrod performance status (PS) scores 0-1 (74%), PS 2 (26%); Okuda stage I (24%) and stage II (76%). Fifteen patients were enrolled in phase I: level 1 (n = 3), level 2 (n = 6), level 3 (n = 6), level 4 (n = 0). Level 2 was identified as the MTD. Dose-limiting toxicities included esophageal bleeding, grade 4 neutropenia and neutropenic fever. Of the 34 patients evaluable for response in phase II (of 35 total), there were four (11.8%) partial responses (95% CI, 0.8% to 22.8%) and six (17.6%) minor responses; nine (26.5%) had stable disease and 15 (44.1%) progressed. Sixteen per cent of patients had a decline of >or=50% in alpha-fetoprotein levels after treatment. Median survival and progression-free survival were 4.6 months (range 0.3-19.2) and 2.5 months (range 0.2-7.8), respectively, for 35 patients. Grade 3/4 hematological toxicities included anemia (45.7%), neutropenia (51.4%), thrombocytopenia (25.7%); febrile neutropenia (11.8%) and non-hematological toxicities were mild to moderate., Conclusions: Gemcitabine plus doxorubicin produces modest activity and moderate toxicity in this cohort of Chinese patients with advanced HCC.

In Southeast Asia and Taiwan, betel quid chewing is prevalent. Patients with head and neck cancer who chewed betel quid habitually seem to experience more severe chemotherapy-induced mucositis in our clinical practice. To validate this issue, patients with untreated head and neck cancer who received cisplatin (cDDP) plus a 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy were included in this analysis. Information on the consumption of betel quid, tobacco, and alcohol were recorded before chemotherapy. Oral submucous fibrosis (OSF) was diagnosed clinically according to the fibrotic appearance of the mucosa and trismus. Mucositis was scored according to the World Health Organization criteria, and the mucositis score of the first course of chemotherapy was used for analysis. From December 1993 to April 1996, 120 patients were enrolled in this trial. Neither the betel quid chewing nor the cancer of the oral cavity was to be a significant factor for mucositis. However, clinically diagnosed OSF was found to display a significant correlation with more severe mucositis (p = 0.02). We concluded that in betel quid chewing-prevalent areas, OSF was a risk factor of more severe mucositis in head and neck cancer patients treated by CDDP and 5-FU-based regimens.

The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count <10 x 10(9)/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count <50 x 10(9)/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1%, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide.

Laboratory medicine and hospital central laboratory system were adopted in Taiwan after World War II. In medical schools, laboratory medicine or clinical pathology teaching is allocated to junior students. Three years of clinical pathology or four years of anatomical pathology training is required for pathology resident. Recent trend indicates that both the hospitals and the young doctors favor the five years combined C.P. (two-years) and A.P. (three years) training program. At present, 75 clinical pathologists and 213 anatomical pathologists are qualified. Approximately 70% of them work in medical centers and medical schools. Consequently, the medium and small size hospitals suffer from serious shortage of pathologist. Studies during the part 50 years indicate substantial difference in the improvement of laboratory medicine and central laboratory before and after 1975. Significant improvement in the working space, facility, equipment, staff, quality control and productivity was evident after 1975. The three health care policies contributing to the overall improvement are: 1. hospital accreditation project, 2. medical care network plan, and 3. medical specialist system.

We evaluated in retrospect the applicability of conservative hepatic resection for hepatocellular carcinoma (HCC) of cirrhotic patients. Eighty (14.6%) of 548 patients with HCC underwent liver resection over a period of 10 years in this hospital. They were divided into two groups according to surgical procedures. In group I, 22 patients underwent major hepatic resection, and in group II, 58 patients underwent conservative liver resection. The operative mortality for patients in group I was 13.6% while it was 3.5% for those in group II. The difference was significant (p<0.05). The five-year survival rate was 22% for patients in group I, while it was 21% for group II patients. The rate of HCC recurrence was 47.4% for group I patients while it was 57.1% for group II patients. The difference was not significant. The tumor-free survival rates at 6-, 12-, 24- and 36-months were 80%, 75%, 55% and 55% respectively for patients in group I, while they were 50%, 42.5%, 42.5% and 42.5% for patients in group II. It suggested that conservative liver resection was associated with early recurrence of HCC. But the difference of mean tumor-free survival time is not significant (35.82+/-5.47 vs 38.63+/-8.05 months, p>0.05). Using Cox's regression analysis, the presence of Child's B was identified as an independent adverse prognostic factor (p=0.000) for long-term survival. The factors associated with poor tumor-free survival rate were Child's classification (p=0.008), metastasis (p=0.021), liver cirrhosis (p=0.039) and tumor size (p=0.054). By evaluating the operative mortality, long-term survival rate, prognostic factors for cumulative survival time and tumor-free survival time, it suggests that conservative liver resection can be selectively used to treat HCC associated with liver cirrhosis.

p53 mutation has been rarely reported in cerebral primitive neuroectodermal tumors (PNET). To determine the significance of p53 mutations in the development of cerebral PNET, we studied cerebral PNET samples from 14 patients, 8 females and 6 males with a mean age of 38 years (range 10 months to 77 years) who had total or subtotal surgical resection. Histological typing of PNET with neuronal (N) and non-neuronal (NN) differentiation groups revealed 8 and 6 cases, respectively. Six (43%) of the 14 patients had p53 mutation. The p53(+) and p53(-) groups had an age range of 19-77 with a mean of 49 years and 10 months to 57 years with a mean of 30 years, respectively. p53 expression between the PNET-N and PNET-NN groups was 5 of 8 (62.5%) and 1 of 6 (16.7%), respectively. The mutations contained 3 transitions, 2 transversions and 1 frameshift; none of them occurred at the site of 'hot-spot' residues (codons 175, 248, 273). The results suggest that: (1) p53 mutation in cerebral PNET tends to show a higher incidence of neuronal differentiation and occurs in the older age group in Taiwan, (2) there was no difference in survival time between the PNET-N and PNET-NN groups (7 months and 6 months) (P = 0.54), and between p53(+) and p53(-) groups (6 months and 7 months) (P = 0.57), and (3) PNET may be an entity of a heterogenous group of tumors with different genetic mechanisms controlling their trends of differential lineage. Further studies are needed to determine the significance of p53 mutations in PNET development, especially the role of carcinogens in the genesis of PNET in Taiwan.

Despite its rarity by routine karyotypic analysis, cryptic t(12;21)(p12-13;q22) translocation leading to TEL/AML1 fusion has been recognized as the most frequent genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) in two recent studies, one from France and the other from the United States. To estimate the frequency of this abnormality in the Chinese population, we studied 41 children with ALL and 17 with acute myeloid leukemia (AML) in two medical centers in Taiwan, using the reverse transcriptase polymerase chain reaction (RT-PCR) assay. Results of this analysis demonstrated a 17% frequency of this translocation in the ALL population overall and 19% in patients with B-lineage ALL, similar to previous findings in Caucasian children. None of the patients with AML had TEL/AML1 fusion transcripts. In addition to its association with the B-lineage immunophenotype, TEL/AML1 was also correlated with a low presenting leukocyte count and favorable age (1-10 years). These findings, combined with earlier reports, indicate that TEL/AML1 fusion is the most frequent genetic abnormality in childhood ALL, regardless of race. Molecular diagnosis of t(12;21)-positive ALL may identify a subgroup of patients who do not require intensive treatment for cure.

The nature and occurrence of gallstones in Taiwan and their etiologic factors might not be the same as in Western countries and warranted a systematic investigation. Gallbladder biles and gallstones were obtained at surgery from 100 and 74 patients, respectively. Common duct bile and stones were either drained through an indwelling common duct T-tube or aspirated through a nasobiliary catheter in 108 patients. Gallstones were analyzed for bilirubin, cholesterol, bile acid, calcium, and residue, and biles for bile acid, cholesterol, phospholipid, bilirubin, and beta-glucuronidase. There were four major kinds of gallstones in Taiwan: cholesterol/mixed stones, high-residue black formed pigment stones, low-residue brown formed pigment stones, and muddy pigment stones. The surgical incidence of all types of stones increased steadily during the past four decades. During the past 15 years the relative frequencies for mixed, formed pigment, and muddy pigment stones had been roughly 40, 40, and 20%, respectively, with a further increase in the mixed stones and a decrease in the muddy pigment stones in recent years. Improvement of nutritional status and living standards might contribute to such changes. Cholesterol content in the common duct and gallbladder biles was higher in the mixed stone group than in other groups. Bacterial beta-glucuronidase activity was detected in 53% of patients with muddy pigment stones. Endogenous beta-glucuronidase activity and concentration were also highest in this group, intermediate in the formed pigment and mixed stone group, and lowest in the control. We concluded that hypercholesterobilia was responsible for increasing incidence of mixed stones during the past two decades, while both bacterial and human beta-glucuronidase might contribute to pigment cholelithiasis.

Our institute serves as a centralized clinical laboratory for municipal and private hospitals in Taipei, a major international metropolis in the Asian region. Two key considerations leading to the development of our toxicology program are: a large number of foreign visitors and local residents returning from overseas trips may bring in chemicals which are less commonly seen in this region; and the lack of readily available assays for a large percentage of commonly used medicines, including prescription and over-the-counter drugs. Our toxicology screening program addresses the needs of both the Emergency Department Drug Screening and Drug of Abuse Screening. In Emergency Department Drug Screening, REMEDi HS is used as the general screening method. In Drug of Abuse Screening, the TDx is used for the initial screening of amphetamine-like substances and opiates, followed by REMEDi HS for the confirmation of positive samples. Emergency Department data collected at our institute over one year (September 1992 to August 1993) identified 57 different drugs in 713 samples. Opiates, narcotics and central stimulants accounted for 24% of the encountered drugs. Presently, there is no extensive reporting of misuse of benzodiazepines in this region. The detection of herbal ingredients like ephedrine and methylephedrine (from the Ma-Huang plant) in patient samples illustrates a large area often overlooked by western toxicology.

During a four-year period from November 1988 to October 1992, 41 cases of bacterial meningitis with a positive cerebrospinal fluid (CSF) culture and/or CSF antigen test were collected at the National Cheng Kung University Hospital. The ages of the subjects ranged from 32 days to 13 years, with a median of seven months. The male to female ratio was 2.4:1. The most common causative agent was Haemophilus influenzae type b (Hib, 29.3%), followed by group B beta-hemolytic streptococci (GBS, 24.4%), Streptococcus pneumoniae (22.0%), Escherichia coli (4.9%), Neisseria meningitidis (4.9%), Salmonella species (4.9%), Klebsiella pneumoniae (4.9%), Pseudomonas aeruginosa (2.6%), and viridans streptococci (2.6%). The onset of GBS meningitis was always prior to four months of age. Of the 41 cases studied, 27 (65.9%) were aged from two months to five years; 12 (44.4%) of these had meningitis caused by Hib. Most of the cases (90.2%) had a fever as the first clinical manifestation. Ampicillin combined with a third-generation cephalosporin was effective against most of the causative pathogens. The most frequently encountered short-term sequelae were seizures (64.7%), subdural effusion (55.9%) and ventriculomegaly (44.1%). Observations on long-term sequelae are ongoing. While the case-fatality rate was as high as 33.3% in S. pneumoniae, and 25% in Hib-infected patients, the overall mortality rate was 17.1%. There is a need for greater emphasis on prevention through the use of available vaccines, including the newly introduced conjugate vaccines against Hib which are capable of eliciting immune responses in infants as young as two months.

To evaluate the age-related changes in the bone remodeling rate, the vitamin D status, and parathyroid function of healthy Chinese women, we selected two serum markers of bone turnover, osteocalcin and alkaline phosphatase (ALP). These markers as well as vitamin D metabolites and parathyrin (parathyroid hormone, PTH) were tested in healthy Chinese female volunteers aged 18 to 80 years residing in the Taipei urban area. The results showed no significant change with aging in the 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and immunoreactive c-terminal PTH (i-cPTH) serum levels. However, there was a trend towards lower 25(OH)D levels at the two extremes of age. The serum levels of 1,25(OH)2D and i-cPTH were comparable with reports of other countries. The serum 25(OH)D levels of our subjects were in general lower than those reported in U.S. white women, but similar to those of European women. The serum osteocalcin levels showed a triphasic change: high in early adulthood, decreasing during the 4th decade of life and then increasing continuously until age 70. After age 70, a decreasing trend was again seen. The serum ALP levels showed a continuous increase from the 3rd to the 8th decade of life. All of the subjects had their bone mineral density (BMD) measured. Linear or polynominal regression analysis as well as multiple regression analysis failed to show a significant correlation between the serum parameters and the BMD measurements at various sites.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study 26 males (average age: 16 y 9 m) and 23 females (average age: 16 y 7 m) were selected from Chungtai Medical Junior College in Taichung, Taiwan. Head films of these students were traced and analysed. Mean values of the Chinese young adults in Taiwan were calculated and the conclusions were as follows: 1) Linear measurements of this present study were compared to Lin's in both males and females. A significant difference was noticed in the skeletal pattern. 2) Angular measurements of this present study were compared to Lin's data of stage IIIC. The gonial angle of this present study was smaller than Lin's data. However, no significant differences were noticed in the positional relationship of upper and lower jaws. 3) Regarding the axes of the anterior teeth, a lingual tipping tendency of the upper anterior teeth and a labial tipping tendency of the lower anterior teeth were observed. 4) The linear measurements in the present study were compared to the Japanese data of stage V. The anterio-posterior dimension of the chinese maxilla was larger than the Japanese. However, there are no significant differences in the position of the upper and lower jaws in females. 5) The measurements of the mandible in this study were smaller than those of the Japanese data. The gonial and mandibular plane angles, especially, were significantly smaller than those of Japanese. 6) The axes of upper and lower anterior teeth of Taiwanese showed more labial tipping than those of Japanese in this study.

Using Moiré topography, the forms of the dental arch and palate of males and females were compared. This was carried out in Fukien province, Taiwan. The materials used consisted of plaster casts of the upper dentitions of 65 males and 69 females with normal occlusion, aged from 20 to 22 years. The results are as follows: 1. The standard form of the upper dental arch represented by a pentagon is shown in Table 1 and in Fig. 3. 2. The dental arch of the male was larger than that of the female, the difference being significant for the anterior and posterior widths of the arch. 3. The correlation coefficients were generally lower in the female than in the male. This was especially true with regard to the size of the anterior portion of the female dental arch. In the posterior portion, there was no correlation between the dental arch length and dental arch width of either sex. 4. The distance from the origin (F) to the papilla incisiva was 23.47 mm in the male and 23.67 mm in the female. The number of moiré band in the bottom of the palate at the origin from the basal plane was 12.89 in the male and 12.73 in the female. There were no significant differences in these two measurements between sexes. 5. On the vertical section of the palate, the anterior portion of the palate of the female was deeper than the male. However, in the posterior portion the male was deeper and wider in the palate morphology than the female. The vertical section in the palate of the male was similar in form to that of the female at the midpoint between the anterior and posterior portions, the canine and/or first premolar. 6. The horizontal section of the palate showed that the distance from the origin to the canine and/or to the first premolar were similar in both sexes at any palate depth.

To investigate the prevalence of hepatitis D virus (HDV) and hepatitis B virus (HBV) infection among intravenous drug abusers in Taiwan, a total of 761 male prisoners, including 680 intravenous drug abusers, were studied for serological markers of HBV and HDV. Questionnaires were distributed to evaluate the risk factors for HDV infection and also to estimate the strength of association among HDV infection and the risk factors. HBV infection was common, and the positive rates of HBV markers between intravenous drug abusers and non-drug abusers were not statistically different. However, the positive rate of the antibody to HDV was significantly higher among intravenous drug abusers than among non-drug abusers (21.3% vs. 8.6%). Of 131 chronic HBV carriers with intravenous drug abuse, 119 (91%) were anti-HD positive. Using multiple logistic regression models, we found that the most important risk factor for HDV infection was hepatitis B surface antigen (HBsAg) carriage, and intravenous drug addiction the next. A matched case-control study also was conducted to compare liver function tests among both anti-HD- and HBsAg-positive group anti-HD-negative, and HBs-AG-positive group as well as those with neither positive. Statistically significant difference in liver function tests was not found. It is concluded that the HBsAg carriers with intravenous drug abuse in Taiwan are commonly HDV infected with and that the infection does not seem to affect the liver as assessed by liver function tests.

The monozygotic (MZ) cotwin control method was employed to elucidate possible environmental determinants of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum cholesterol and triglyceride levels. A population-based twin sample of 73 male and 77 females MZ twin pairs was recruited from 12 junior high schools in Taipei city. Intrapair differences in blood pressure were negatively associated with intrapair difference in vegetable preference, attaining significance for DBP in males and SBP in females. Cholesterol was positively associated with milk consumption and preference for sweets, fried foods, meat and fish. A negative association was also observed between cholesterol and vegetable preference. These associations for cholesterol were significant in males only. Triglyceride level negatively associated with preferences for sweets and vegetable, attaining significance for vegetables in both males and females and for sweets in males only.

Several cases of parkinsonism were found in a ferromanganese smelter after the ventilation system had broken down and had not been repaired for eight months in 1985. To determine the aetiology and prevalence of parkinsonism, 132 workers were submitted to thorough medical examination and estimated air concentrations of carbon monoxide and manganese at different worksites. Only six of eight workers performing electrode fixation or welding during 1985 developed parkinsonism. They were exposed for 30 minutes each day, seven days a week, to high concentrations of air manganese (greater than 28.8 mg/m3). There was a consistent trend between the index of exposure to manganese and signs and symptoms exhibited by extrapyramidal systems. After repair of the ventilation system, the air concentration of manganese during electrode fixation and welding decreased to less than 4.4 mg/m3; furthermore, no new cases of parkinsonism have been observed. Workers with parkinsonism recovered partially after removal from original worksites and treatment with levodopa. It is concluded that the outbreak resulted from exposure to high concentrations of manganese fumes through the breakdown of the ventilation system.

In order to estimate genetic variance and heritability of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum cholesterol and triglyceride levels, a total of 235 (79 male and 82 female MZ, 41 male and 33 female DZ) twin pairs, recruited from 12 junior high schools in Taipei city, were studied. Statistically significant genetic variance observed for SBP, DBP, serum cholesterol and triglycerides persisted after adjustment for age and anthropometric characteristics. However, further adjustment for dietary preference, beverage consumption, and other host and environmental factors gave different results: genetic variance of adjusted SBP and DBP was still significant, while significance was found only in males for cholesterol and in neither males nor females for triglycerides. Heritability estimates of unadjusted SBP, DBP, cholesterol and triglycerides were 0.27, 0.45, 0.21 and 0.41, respectively, for males, and 0.15, 0.42, 0.41 and 0.82, respectively, for females. After adjustment for age, anthropometric characteristics, host and environmental factors, the heritability estimates of SBP, DBP and cholesterol were 0.64, 0.72 and 0.50, respectively, for males, and 0.40, 0.60 and 0.37, respectively, for females.

The purpose of this study was to determine the influence of parental occupational lead exposure on the lead levels of newborn cord blood in the Taipei area. From September 1984 to June 1985, 5,000 pregnant women voluntarily participated in the study at the Taipei Municipal Maternal and Child Hospital. Each woman was interviewed regarding her and her husband's occupational exposures; 2,948 successfully delivered healthy newborns, and cord blood samples were obtained using Terumo Venoject, and 242 samples were analyzed by graphite furnace atomic absorption spectrometry using an Instrumentation Laboratory 251 instrument. Nine cord blood samples were from newborns with both parents exposed, 26 samples had maternal exposure only, 105 samples had paternal exposure only, and 102 were nonexposed. The results showed that the average lead level of cord blood with both parents exposed was 8.9 +/- 2.9 micrograms%, maternal exposure 9.0 +/- 3.8 micrograms%, paternal exposure 8.3 +/- 3.4 micrograms%, and 6.9 +/- 3.2 micrograms% in the nonexposed group. There were significant differences between the nonexposed and the maternal exposure groups, and also between the nonexposed and paternal exposure groups. All 26 maternal exposures were from lead soldering operations. Multivariate analysis revealed that, after control of father's exposure status, newborn cord blood lead level increased 0.27 micrograms% for each hour the mother spent on lead soldering during a normal working day, thus suggesting that soldering during pregnancy may be hazardous to newborns. Paternal contribution to the cord blood lead levels seemed to be through either working at home with the pregnant mother also at home or bringing work clothes home for laundering.

To determine the influence of ventilation control and work practices on the health of workers potentially exposed to organophosphate and carbamate compounds, we examined a total of 989 employees from pesticide factories in Taiwan during 1986-1987. Each employee was examined by a physician, and a blood sample was drawn for plasma cholinesterase, complete blood count, and liver and renal function tests. Forty-one employees with medical conditions that might alter the plasma cholinesterase were excluded. Results showed that 43 of 515 production employees had decreased plasma cholinesterase as compared with four of 340 non-production employees. Production employees working under adequate ventilation control seemed to have a lower prevalence of decreased plasma cholinesterase than those under inadequate ventilation control, although the difference was not statistically significant (p = 0.242). There was a significant association between the level of housekeeping and work practices and the prevalence of decreased plasma cholinesterase (p = 0.022). We conclude that inadequate ventilation control and poor work practices may create a potential danger of pesticide poisoning among production employees in Taiwan and should be corrected immediately.

A population-based sample of 73 male and 77 female monozygotic (MZ), and 41 male and 33 female dizygotic (DZ) Chinese adolescent twin pairs were studied to assess effects of gene-environment interactions of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum cholesterol and triglyceride levels. Intrapair concordance in BP levels was found to be significantly associated with the interaction of zygosity and salty foods preference and also with that of zygosity and vegetable preference. A consistently positive and statistically significant association was observed between the intrapair difference in serum cholesterol and the interaction of zygosity and animal organ preference; while intrapair concordance in serum cholesterol was associated with the interaction of zygosity and milk consumption. Intrapair difference in serum triglycerides was associated with the interaction of zygosity and fish preference, and a significant association was also found between the intrapair concordance in serum triglycerides and the interaction of zygosity and sweets preference. These observations suggest that the impact of these environmental agents may be influenced by the genotype.