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In early 2020 from April to early June, the metropolitan area of Sydney as well as the rest of New South Wales (NSW, Australia) experienced a period of lockdown to prevent the spread of COVID-19 virus in the community. The effect of reducing anthropogenic activities including transportation had an impact on the urban environment in terms of air quality which is shown to have improved for a number of pollutants, such as Nitrogen Dioxides (NO2) and Carbon Monoxide (CO), based on monitoring data on the ground and from a satellite. In addition to primary pollutants CO and NOx emitted from mobile sources, PM2.5 (primary and secondary) and secondary Ozone (O3) during the lockdown period will also be analyzed using both statistical methods on air quality data and the modelling method with emission and meteorological data input to an air quality model. By estimating the decrease in traffic volume in the Sydney region, the corresponding decrease in emission input to the Weather Research and Forecasting—Community Multiscale Air Quality Modelling System (WRF-CMAQ) air quality model is then used to estimate the effect of lockdown on the air quality especially CO, NO2, O3, and PM2.5 in the Greater Metropolitan Region (GMR) of Sydney. The results from both statistical and modelling methods show that NO2, CO, and PM2.5 levels decreased during the lockdown, but O3 instead increased. However, the change in the concentration levels are small considering the large reduction of ~30% in traffic volume.

The 2019–2020 summer wildfire event on the east coast of Australia was a series of major wildfires occurring from November 2019 to end of January 2020 across the states of Queensland, New South Wales (NSW), Victoria and South Australia. The wildfires were unprecedent in scope and the extensive character of the wildfires caused smoke pollutants to be transported not only to New Zealand, but also across the Pacific Ocean to South America. At the peak of the wildfires, smoke plumes were injected into the stratosphere at a height of up to 25 km and hence transported across the globe. The meteorological and air quality Weather Research and Forecasting with Chemistry (WRF-Chem) model is used together with the air quality monitoring data collected during the bushfire period and remote sensing data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellites to determine the extent of the wildfires, the pollutant transport and their impacts on air quality and health of the exposed population in NSW. The results showed that the WRF-Chem model using Fire Emission Inventory (FINN) from National Center for Atmospheric Research (NCAR) to simulate the dispersion and transport of pollutants from wildfires predicted the daily concentration of PM2.5 having the correlation (R2) and index of agreement (IOA) from 0.6 to 0.75 and 0.61 to 0.86, respectively, when compared with the ground-based data. The impact on health endpoints such as mortality and respiratory and cardiovascular diseases hospitalizations across the modelling domain was then estimated. The estimated health impact on each of the Australian Bureau of Statistics (ABS) census districts (SA4) of New South Wales was calculated based on epidemiological assumptions of the impact function and incidence rate data from the 2016 ABS and NSW Department of Health statistical health records. Summing up all SA4 census district results over NSW, we estimated that there were 247 (CI: 89, 409) premature deaths, 437 (CI: 81, 984) cardiovascular diseases hospitalizations and 1535 (CI: 493, 2087) respiratory diseases hospitalizations in NSW over the period from 1 November 2019 to 8 January 2020. The results are comparable with a previous study based only on observation data, but the results in this study provide much more spatially and temporally detailed data with regard to the health impact from the summer 2019–2020 wildfires.

The Djumbodis™ dissection system was introduced as an alternative to aortic arch replacement in acute type A aortic dissection involving the arch. In our own experience, some patients with Djumbodis implantation developed distal aortic arch and descending aortic aneurysm during subsequent follow-up and required additional interventions. However, as there is a high incidence of fracture associated with the Djumbodis system, further endovascular interventions are not feasible. We report a case of successful open descending aortic replacement in a patient with a fractured Djumbodis stent system.

The purpose of this study was to determine factors associated with self-perceived body image in female patients with head and neck cancer (HNC), and factors associated with healthcare professional's rating of disfigurement, as well as the correlation between patient and observer ratings. This cross-sectional study recruited 105 women with HNC at a large medical centre. Measures of facial disfigurement and body image, as well as demographic and clinical characteristics, were collected. Multivariate multiple linear regression modelling was used to identify factors associated with healthcare professional's rating of disfigurement and patient self-perceived body image. Disfigurement ratings by healthcare professionals were positively associated with patient self-perceived body image. Medical treatment, cancer stage, radiation dose and cancer site were significantly associated with disfigurement. Medical treatment was an important predictor of perceived body image. These findings indicate a moderate prevalence of disfigurement among women with HNCs. Patients with more disfigurement were more likely to have dissatisfaction with their body image. Nursing professionals need to carefully assess the appearance of women with HNC. Camouflage interventions can be used to help appropriately cope with the disfigurement, and to achieve improved satisfaction with their body image.

The development of nonhuman primate (NHP) embryonic stem cell (ESC) models holds great promise for cell-mediated treatment of debilitating diseases and to address numerous unanswered questions regarding the therapeutic efficacy of ESCs while supplanting ethical considerations involved with human studies. Here we report successful establishment and characterization of 3 novel baboon (Papio cynocephalus) ESC lines from the inner cell mass of intracytoplasmic sperm injection-derived blastocysts. Embryos were cultured in an improved baboon embryo in vitro culture protocol. The inner cell mass of blastocyst was laser-dissected and plated on mouse embryonic fibroblast feeder cell monolayer in the NHP ESC culture medium. Three cell lines with characteristic ESC morphology have been cultured through an extended period (14 months), with 2 male cell lines (UT-1 and -2) and 1 female cell line (UT-3) displaying normal baboon karyotypes. Reverse transcription-polymerase chain reaction analysis confirmed that all 3 lines express primate ESC pluripotency markers, including OCT-4, NANOG, SOX-2, TERT, TDGF, LEFTYA, and REX-1. All 3 lines demonstrated positive immunocytochemical staining for OCT-4, stage-specific embryonic antigen-3, stage-specific embryonic antigen-4, TRA-1-60, and TRA-1-81. Baboon ESCs injected into NOD/SCID mice formed teratomas with all 3 germ layers. In addition, embryoid body-like spherical structures were derived and initial outgrowth was observed when embedded into extracellular matrix Matrigel. The ESC lines established in this NHP model have the potential to extend our knowledge in the fields of developmental biology, regenerative medicine, and future applications, including preclinical safety assessment of in vivo stem cell therapy.

Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cells using small interfering RNAs (siRNA). To accomplish this, we developed nine siRNAs against either the E6 or E7 genes of HPV-16 or HPV-18 in several combinations, yielding siRNAs targeting 16E6, 16E7, 18E6 and 18E7. We measured the effectiveness of the siRNAs by examining E6 or E7 mRNA expression after transfection of the siRNAs into HPV-positive CaSki (HPV-16) or HeLa (HPV-18) cell lines. We found that the HPV-siRNAs significantly reduced cell growth and colony formation in both cell lines. Flow cytometry analysis revealed a significant increase in apoptosis. The siRNAs had no effect on cell growth, colony formation or apoptosis in HPV-negative C33A cells, demonstrating a lack of off-target effects. In addition, an in vivo xenograft study showed that intra-tumoral injection of the siRNAs reduced tumor growth in BALB/c nude mice. In conclusion, we have developed highly specific and potent HPV-siRNAs that successfully suppress tumor growth and induce apoptosis in HPV-positive cervical cancer cells. siRNA treatment has potential for further development as an adjuvant therapy for cervical cancer.

Human papillomavirus (HPV) infections are deemed to play a role in the pathogenesis of oral cavity cancer (OCC). However, their exact prevalence and clinical significance remain unclear. Herein, we investigated the prevalence and prognostic value of HPV infections in a large sample of Taiwanese OCC patients. This study was designed as a retrospective cohort study. Between 2004 and 2011, we identified 1002 consecutive patients with newly diagnosed OCC who were scheduled for standard treatment. HPV genotyping was performed in tumor specimens using polymerase chain reaction-based HPV blots. To investigate the temporal trends of HPV infections and their impact on 5-year overall survival (OS), patients were divided into 2 cohorts according to calendar periods: “2004 cohort” (2004–2007; n = 466) and “2008 cohort” (2008–2011; n = 536). Univariate and multivariate Cox regression models were also used to identify the independent predictors of OS in the 2 cohorts. A weighted risk score was assigned to each factor based on the range of their corresponding hazard ratios and validated in both cohorts using the c-statistic. The overall prevalence of HPV infections was 19%, with a trend toward decreasing rates from 2004 to 2011. In patients without risky oral habits, the 5-year OS rate of HPV-positive patients was significantly lower than that of HPV-negative cases (49% vs 80%; P = 0.021). In the 2004 cohort, multivariate analysis identified HPV16, pathological T3/T4, pathological N1/N2, and extracapsular spread as independent adverse prognostic factors for OS. In the 2008 cohort, pathological N1/N2, pathological stage III/IV, and histological tumor depth >8 mm were identified as independent adverse prognostic factors. Using a weighted grading system incorporating HPV16 infection, we devised a prognostic index that identified 4 distinct risk categories with 5-year OS rates ranging from 25% to 89% (c-statistic = 0.76) in the 2004 cohort. The validity of the index was internally confirmed in the 2008 cohort (c-statistic = 0.71). We conclude that HPV infections are common in Taiwanese OCC patients and predict 5-year OS. If independently validated, our composite prognostic score comprising HPV16 infection may be useful for allocating OCC patients to risk-adapted therapies.

Purpose: To report on fluoroscopically guided percutaneous gastrostomy (FPG) using a modified gastropexy technique with the insertion of a large‐bore balloon‐retained gastrostomy catheter in patients with head and neck tumors. Material and Methods: Thirty‐four patients with head and neck tumors underwent a modified gastropexy with two T‐fasteners followed by the insertion of a 14‐F balloon‐retained catheter through a peel‐away introducer. The success rate and the complications of the procedures were evaluated at 14 days, 30 days, and 60 days. The complications were classified as: major complications that necessitated intensive and/or surgical treatment; minor complications that could be treated conservatively; and tube‐related complications manageable by tube exchange. Results: FPG was technically successful in all cases. There were no major complications, two minor complications where superficial stoma infection was controlled by antibiotics, three minor tube‐related complications, all three easily managed by catheter replacement via the original tract. Conclusion: FPG with insertion of a large‐bore balloon‐retained catheter using a modified gastropexy technique is a safe and effective method that creates a feeding access for patients with head and neck tumors and esophageal obstruction. Minor complications can be managed conservatively. FPG may be a good alternative to surgical or percutaneous endoscopic gastrostomy.

The Wnt/β-catenin signaling pathway has emerged as a key regulator of complex biological processes, such as embryonic development, cell proliferation, cell fate decision and tumorigenesis. Recent studies have shown that the deregulation of Wnt/β-catenin signaling is frequently observed and leads to abnormal cell growth in human breast cancer cells. In this study, we identified a novel regulatory mechanism of Wnt/β-catenin signaling through RARRES3 that targets and modulates the acylation status of Wnt proteins and co-receptor low-density lipoprotein receptor-related protein 6, resulting in the suppression of epithelial–mesenchymal transition and cancer stem cell properties. Mutation of the conserved active site residues of RARRES3 indicates that RARRES3 serves as an acyl protein thioesterase that tethers its target proteins and modulates their acylation status. Furthermore, the functions of p53 in cell proliferation and Wnt/β-catenin signaling are significantly associated with the induction of RARRES3. Thus our findings provide a new insight into the molecular link between p53, protein acylation and Wnt/β-catenin signaling whereby RARRES3 plays a pivotal role in modulating the acylation status of signaling proteins.

The objective of this study was to test the hypothesis that neurodevelopmental outcome would differ between two groups of small-for-gestational age infants born at term showing different in utero growth characteristics during the third trimester. The design was a prospective cohort study done at a tertiary referral centre. The 76 subjects who fulfilled the inclusion criteria had an estimated fetal weight below the 10th centile for their gestation. Subsequent to enrolment, repeat ultrasound scans were performed weekly to determine growth velocity. Twenty-three infants whose change in fetal abdominal circumference between first and last scan was greater than -1.5 standard deviation scores (SDS) were assigned to the intrauterine growth retardation group (IUGR) while 53 infants whose fetal abdominal circumference changed less than 1.5 SDS were assigned to the small-for-gestational-age (SGA) group. Ten infants with normal intrauterine growth were enrolled as controls. Following delivery all infants had a neurological examination and a cranial ultrasound scan. At 1 year, 75 infants (87%) were traced and reassessed (49 SGA, 18 IUGR and eight controls) with a neurological examination and a developmental assessment. At birth, impairments were found in 27 (51%) of the SGA, 13 (57%) of the IUGR groups and one (10%) of the controls. At 1 year, 18 (37%) of the SGA subjects, six (33%) of the IUGR subjects and one (13%) of the control infant were impaired, including three (6%) of the SGA subjects and one (6%) of the IUGR subjects who were disabled. We conclude that in term fetuses with an estimated birthweight below the 10th centile for their gestation, the pattern of growth in the third trimester does not affect outcome at 1 year. In spite of optimum obstetric management, nearly one-third of the combined SGA and IUGR term fetuses had suffered some, albeit minor, neurological damage.

OBJECTIVE. The purpose of this study was to evaluate the efficacy of Wallstents in treating inferior vena cava obstruction in hemodialysis patients. CONCLUSION. For the short and intermediate term, percutaneous placement of inferior vena cava Wallstents, followed by balloon angioplasty, is a safe and valuable technique for preserving the often limited central venous access in hemodialysis patients. To maintain patency, recurrent stenosis within the Wallstent can be treated with additional angioplasty.

The new allele, HLA-B*07:162, is identical to HLA-B*07:12 in exon 2 but has a non-synonymous substitution at position 419 (A to C) in exon 3.

The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain.The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests.Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers (P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy.There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result.

Doppler ultrasound has been advocated as a useful tool to evaluate pregnancies with intrauterine growth retardation (IUGR). However, many previous studies have used smallness for gestational age (SGA) at birth to define IUGR. The ability of Doppler ultrasound to predict SGA, neonatal morphometric indices of wasting such as a low ponderal index, and perinatal morbidity is reviewed. Doppler assessment of the umbilical and uteroplacental vasculatures were inferior to ultrasound measurements of fetal size in the prediction of SGA. In low risk fetuses, umbilical artery waveform indices were of limited value in the prediction of neonatal morphometric indices of wasting. Within a group of high risk fetuses, Doppler assessment of the umbilical artery and, in particular, the middle cerebral and aortic vessels, were useful in predicting fetuses with neonatal wasting. Similar findings were noted in the prediction of perinatal morbidity. The review confirms the usefulness of umbilical artery Doppler waveform indices in the antenatal assessment of IUGR. Whilst preliminary studies appear to suggest that Doppler waveform indices of the middle cerebral and aortic vessels may confer an additional advantage in the antenatal assessment of IUGR, randomized controlled trials evaluating their effect on perinatal outcome and studies on the reproducibility of these indices need to be carried out before their widespread introduction into obstetric practice.

In a prospective observational study, the fatty acid content of human umbilical artery and vein wall phospholipids was determined in fetuses classified according to their change in abdominal circumference during the third trimester. Three groups were identified: appropriate for gestational age (AGA; 24 infants) and small for gestational age (SGA; 38 infants) with normal antenatal growth rate, and SGA with fetal growth retardation (22 infants). The venous linoleic acid (18:2 omega 6) content (expressed as a percentage of the total fatty acids identified) was greater in growth retarded SGA fetuses (3.5 (0.6)%) than in SGA fetuses with a normal growth rate (3.1 (0.5)%) and AGA fetuses (3.0 (0.5)%), whereas the venous contents of eicosatrienoic (20:3 omega 6) and docosahexaenoic acid (22:6 omega 3) were lower. In growth retarded SGA fetuses, the venous and arterial 20:3 omega 6 content correlated with the change in abdominal circumference. In SGA fetuses with a normal growth rate, lower contents of arterial 18:2 omega 6 and 22:6 omega 3 were associated with a smaller change in abdominal circumference and birth weight. Different metabolic derangements appear to underly normal and subnormal growth rate in SGA fetuses, suggesting that different strategies of dietary intervention may be required to aid fetal growth and reduce the sequelae of fetal growth retardation.

We used the IMNpRH2(12,000-rad) RH and IMpRH(7,000-rad) panels to integrate 2019 transcriptome (RNA-seq)-generated contigs with markers from the porcine genetic and radiation hybrid (RH) maps and bacterial artificial chromosome finger-printed contigs, into 1) parallel framework maps (LOD ≥ 10) on both panels for swine chromosome (SSC) 4, and 2) a high-resolution comparative map of SSC4, thus and human chromosomes (HSA) 1 and 8. A total of 573 loci were anchored and ordered on SSC4 closing gaps identified in the porcine sequence assembly Sscrofa9. Alignment of the SSC4 RH with the genetic map identified five microsatellites incorrectly mapped around the centromeric region in the genetic map. Further alignment of the RH and comparative maps with the genome sequence identified four additional regions of discrepancy that are also suggestive of errors in assembly, three of which were resolved through conserved synteny with blocks on HSA1 and HSA8.

Screening in ovarian cancer is progressively finding out candidate genes and proteins which may work as screening biomarkers and play a role in tumor progression. We examined the protein expression patterns of ovarian cancer tissues using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of fight mass spectrometry (MALDI-TOF MS).Tissues from 36 ovarian cancers and 20 normal ovaries were examined by 2-DE. The images of silver stained gels were analyzed by ImageMaster 2D Elite. The peptide mixtures, after in-gel digestion, were determined by MALDI-TOF MS for fingerprinting. The de-isotope tryptic peptide profiles were matched by using the Mascot search engine based on the entire NCBI and Swiss-Prot protein databases. Western/dot blots were then applied to verify the findings.In ovarian cancer, 12 proteins that showed differential expressions were identified unequivocally. Among these proteins, five proteins (galectin-1, cathepsin B, ubiquitin carboxy-terminal hydrolase L1, HLA class II antigen DRB1-11 and heat shock protein 27) were up-regulated and seven proteins (cellular retinol-binding protein, transthyretin, SH3 binding glutamic-rich-like protein, tubulin-specific chaperone A, DJ-1, gamma-actin and tropomyosin 4) were down-regulated.The present study is the first to report the up-regulation of ubiquitin carboxy-terminal hydrolase L1 and the down-regulation of SH3 binding glutamic-rich-like protein, tubulin-specific chaperone A, and tropomyosin 4 in human ovarian cancer tissues. Further cloning and functional analysis of these salient proteins will provide more information on their pathophysiologic roles in ovarian cancer.

DDX3Y (also known as DBY) is a member of the DEAD box protein family, which is involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation. In the human, DDX3Y is located in the AZFa interval in the Y chromosome. Deletion of the AZFa region has been shown to disrupt spermatogenesis, causing subfertility and infertility in otherwise healthy men. Here, we report the characterization of the bovine (b) DDX3Y gene and its homologs DDX3X and PL10. We found 2 transcripts for the bDDX3Y (bDDX3Y-L and -S), which correspond to the long and short transcripts of the human DDX3Y and mouse Ddx3y gene. The 2 transcripts are identical except for a 3-bp (AGT) insertion at the position of nt 2025 and an expanded 3'UTR (nt 2155-2769) in bDDX3Y-L. The bDDX3Y-S encodes a peptide of 660 amino acids (aa), while the bDDX3Y-L encodes a peptide of 661 aa as the result of an additional serine (S) insertion at the position of aa 634. Both bDDX3Y isoforms contain the conserved DEAD-box motif. The bDDX3Y is composed of 17 exons. The homologous gene on the X chromosome, bDDX3X, is highly conserved to the Y-copy at mRNA (83%) and protein (88%) levels as well as in the genomic structure. The autosomal copy, bPL10, mapped on BTA15, is a processed pseudogene with a similarity of 88.1% to bDDX3Y and 93.7% to bDDX3X mRNA, suggesting that PL10 is a retroposon of DDX3X. RT-PCR analyses showed that bDDX3Y-L, -S, bDDX3X and bPL10 were all widely expressed with predominant expression in testis and brain. Testicular section in situ hybridization revealed that sense and anti-sense RNAs of bDDX3Y-L, -S, and bDDX3X were expressed in interstitial cells. These results together with the finding that the pseudogene bPL10 is transcriptionally active in this study provide a basis for further investigating the DDX3 gene function in spermatogenesis, male fertility and gene evolution in mammals.

2-methoxyestradiol (2-ME), an endogenous estradiol metabolite, has potent antiproliferative effects on cancer cells. However, its usefulness for treating endometrial cancer has not yet been fully explored. We investigated for the first time whether in vitro combinations of 2-ME with various chemotherapeutic agents might result in a synergistic inhibitory effect on the proliferation of human endometrial cancer cells.As a model, two different human endometrial cancer cell lines, HEC-1-A and RL95-2, were used. These cells were treated with 2-ME alone or in combination with paclitaxel, cisplatin, or doxorubicin. Measurements to detect an antiproliferative effect were performed after 24, 48, and 72 hours using the MTT assays.In both endometrial cancer cell lines a significant synergistic effect of 2-ME with paclitaxel was observed. The combination of 2-ME and cisplatin was not synergistic and provided only additive effects. The antiproliferative effect of 2-ME was somewhat antagonized by doxorubicin.Our study shows that 2-ME has a direct antiproliferative effect on endometrial cancer cells. Our results also show a potential anticancer synergy between 2-ME and paclitaxel in vitro. On the other hand, no remarkable synergistic actions were observed between 2-ME and doxorubicin, suggesting that 2-ME may selectively enhance the anticancer actions of certain chemotherapeutic agents in human endometrial cancer. Therefore, combination therapy should be investigated further as an additional therapeutic option for advanced or recurrent endometrial cancer.

The objective of this retrospective study was to investigate prognostic variables and impact of adjuvant therapy in uterine carcinosarcoma.The clinical information and pathological confirmation were reviewed for cases with uterine carcinosarcoma from 1984 to 2005. A total of 45 patients were eligible for analysis.The median follow-up for survivors was 84 months. Five-year overall survival and progression-free survival (PFS) rates were 36.5% and 33.8%, respectively for Stage I-IV. Distant site metastasis with/without pelvic failure occurred in 83.3% of those with recurrence/progression. By multivariate analysis, older age (p = 0.001) and more than half of myometrial invasion (p = 0.002) were significant predictors of death, while only myometrial invasion (p = 0.022) was significantly associated with PFS. Stratified analyses demonstrated a monotonic trend of chemotherapy or chemoradiation to decrease death.Our results suggested that age and depth of myometrial invasion were significant prognostic factors, and chemotherapy or chemoradiation seemed to be beneficial for uterine carcinosarcoma.

To evaluate the outcome and prognostic factors of patients with supraclavicular lymph node (SCLN) involvement at primary diagnosis.We reviewed the medical records of cervical cancer patients primarily treated at Chang Gung Memorial Hospital between 1987 and 2005. Thirty-three patients with histologically confirmed SCLN metastasis at primary diagnosis were eligible for analysis. Clinical and pathological features were analyzed for association with outcome.The 3- and 5-year survival rates of patients with SCLN metastasis were 16.5% and 16.5%, respectively. Multivariate analysis showed the serum level of squamous cell carcinoma antigen (SCC-Ag)15 ng/ml at initial diagnosis (p = 0.021) and staging/restaging including [18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (p = 0.006) to be associated with a better prognosis.Primary SCLN metastasis in cervical cancer is not incurable. The benefit from PET findings might help in selecting appropriate patients for curative primary and/or salvage treatment.

The purpose of this study was to determine the value and cost of obtaining routine chest radiographs after image-guided placement of internal jugular central venous catheters.We reviewed the records of 424 patients in whom 572 internal jugular catheters were placed by sonographic and fluoroscopic guidance over a 2-year period. Inspiratory and expiratory chest radiographs obtained immediately after each procedure were also reviewed.Routine postprocedural chest radiographs revealed no complications and did not alter the treatment of any patient. Delayed pneumothorax was detected after placement of two catheters (0.5%) when patient symptoms prompted additional radiographs.Immediate postprocedural chest radiographs are not routinely needed after image-guided insertion of internal jugular central venous catheters and unnecessarily add to the cost of patient care.

We report a case of a 47-year-old woman with a false-positive [18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) result caused by retained gauze during resection of liver metastasis for a Stage IV ovarian cancer at primary cytoreductive surgery. She achieved complete remission and remained free of progression for seven years. Owing to elevation of CA-125, computed tomography and PET studies were performed, and both showed two potentially resectable lesions. One was located ventral to the diaphragmatic surface of the left hepatic lobe and the other was around the gauze at the right hepatorenal fossa. During surgical intervention, the left supraheptic tumor was excised and the gauze with surrounding granulation was removed. However, the former proved to be recurrent ovarian cancer with the latter proven false-positive. This case demonstrates that PET results should be interpreted with caution in differentiating a benign inflammatory process from malignant abnormalities, especially in regions with a high probability of granulomatous lesions.

The present study was designed to examine whether different p53 haplotypes of exon 4-intron 3-intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) = 1.98; 95% confidence interval (CI), 1.10-3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR = 10.56; 95% CI, 1.23-234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.

Combination chemotherapy for the treatment of gestational trophoblastic tumours (GTT) has been connected with an increased risk of developing secondary tumors (Berkowitz and Goldstein 2009). This r...

Purpose: Supraclavicular lymph node metastasis in breast cancer patients has a poor prognosis, and aggressive local treatment has usually resulted in severe morbidity. The purpose of this study was to select high-risk neck metastasis patients for prophylactic radiotherapy. Methods: Between 1990 and 1998, 2658 consecutive invasive breast cancer patients underwent surgery and adjuvant therapy in the hospital. The median age was 47 years (range 22–92). The median follow-up period was 39 months. The following factors were analyzed: age, tumor size, tumor location, histologic type, histologic grade, estrogen and progesterone receptor status, DNA flow cytometry study results, number of positive axillary lymph nodes, use of chemotherapy, radiotherapy, and/or hormonal therapy, and level of involved axillary nodes. Results: Of the 2658 patients, 113 (4.3%) developed supraclavicular lymph node metastasis during this period. Young age (≤40 years), tumor size >3 cm, high histologic grade, angiolymphatic invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4 positive nodes, and level II or III involved nodes were all significant for predicting neck metastasis in the univariate analysis. Three predictive factors were significant after multivariate analysis: high histologic grade, >4 positive nodes, and axillary level II or III involved nodes. In patients with axillary level I involved nodes and ≤4 positive nodes, the incidence was 4.4%. If axillary level III was involved, the rate of supraclavicular lymph node metastasis was 15.1%. Conclusion: The incidence of supraclavicular lymph node metastasis was higher in the groups with >4 positive nodes and in those with axillary level II or III involved nodes. Selective use of comprehensive radiotherapy for these high-risk patients will achieve good locoregional control.

Graves' disease (GD) is the most common hyperthyroid disorder, but the therapeutic strategy for choosing between medical or ablative therapy has not been standardized. Thyroid hypervascularity is an important diagnostic feature in GD. This study collected Doppler ultrasonography data from patients with GD, Hashimoto's thyroiditis, and simple goiter to develop a hemodynamic index for use in the evaluation of when antithyroid drugs (ATDs) should be withdrawn or ablative therapy given in GD.Thyroid Doppler ultrasonography was used to measure the resistive index (RI) and pulsatility index (PI) in various thyroid diseases. We studied 88 patients, including 13 untreated GD patients, 14 euthyroid GD patients after withdrawal of ATDs for more than 12 months, 14 euthyroid GD patients with normal thyroid stimulating hormone (TSH) concentrations after regular ATD treatment for 12 months (well controlled), 16 hyperthyroid GD patients with undetectable TSH concentrations after regular ATD treatment for more than 12 months (poorly controlled), 13 Hashimoto's thyroiditis patients, and 18 patients with simple goiters.The PI and RI were significantly different between patients with untreated (median PI/RI 1.36/0.79) or medically well-controlled (median PI/RI 0.66/0.51) GD, but no significant differences in PI and RI were found between patients with untreated or medically poorly controlled (median PI/RI 1.24/0.74) GD. An RI cut-off of at least 0.7 with undetectable TSH was found to be suggestive of the need for ablative therapy in GD patients who had received regular ATD treatment for more than 12 months, because of its statistically high sensitivity and specificity in all untreated and poorly controlled GD patients. An RI of less than 0.6 with normal TSH was suggestive of the need for withdrawal of ATDs in GD patients receiving regular medical treatment, because of its statistically high sensitivity and specificity in all treated euthyroid GD patients.This study has developed an RI-derived hemodynamic index that determines the need for ablative or ATD therapy in patients with GD. A large-scale, prospective study is needed to confirm its clinical value.

The treatment of isolated hepatic metastasis from carcinoma of the uterine cervix has yet to be established. We tested the efficacy of percutaneous injection of ethanol and acetic acid as a curative-intent treatment modality for this rare event.Under real-time sonographic guidance, two patients with a solitary hepatic metastasis from carcinoma of the cervix were treated with 99.5% percutaneous ethanol injection (one patient) and 50% percutaneous acetic acid injection (the other patient). The treatment was repeated weekly if laboratory data permitted and aspiration cytology interpreted on site showed tumor cells. Cytology after complete treatment showed no residual tumor cells in either case. Both patients had no evidence of disease during follow-up for 12 and 24 months, respectively.Treatment was successful in two patients with isolated hepatic metastatic lesions from carcinoma of the cervix who received percutaneous injection of 99.5% ethanol or 50% acetic acid.

Fine-needle aspiration cytology (FNAC) is an important method in the evaluation of goiter. However, difficulties are encountered when using this technique to distinguish Hashimoto's thyroiditis from thyroid lymphoma. This study sought to determine the diagnostic sensitivity of FNAC and to determine the effectiveness of chemotherapy in the treatment of thyroid lymphoma.We retrospectively reviewed the clinical manifestations, diagnostic methods, treatment, and prognosis in 14 consecutive patients with histopathology-verified thyroid lymphoma treated in National Taiwan University Hospital from 1981 to 2000.Eleven of the 14 patients underwent FNAC, which identified six lymphomas, one anaplastic carcinoma, three cases of Hashimoto's thyroiditis, and one case of Riedel's struma. Because all cases were promptly biopsied, the mean survival times for patients with or without the correct initial diagnosis (15 mo vs 43 mo) did not differ significantly (p = 0.098 by Student's t-test). Thyroid lymphoma was diagnosed before 1990 in four patients, three of whom were treated with local radiotherapy and one with surgical resection. The mean survival time of these four patients was 60 days. Thyroid lymphoma was diagnosed after 1990 in 10 patients, nine of whom underwent systemic chemotherapy, with additional adjunctive radiotherapy in three patients. The mean survival time in the nine of these 10 patients with follow-up was 60 months. A significant difference was found in the mean disease-free survival times between patients treated before and after 1990 (60 d vs 60 mo, p = 0.005).In this study, FNAC had a sensitivity of only 55%, its major limitation being misdiagnosis of lymphoma as Hashimoto's thyroiditis in three patients. However, such initial misdiagnosis does not affect the prognosis if promptly corrected by histopathology. As evidenced by the improved survival of patients receiving chemotherapy after 1990, we conclude that chemotherapy is effective in the treatment of thyroid lymphoma.

Although diffuse toxic goiter is a classical feature of Graves' disease (GD) nodular goiters are occasionally found in some patients. The aim of the present study was to investigate the ultrasonographic and corresponding cytological manifestations in GD patients with nodular lesions to decide on a therapeutic strategy. Twenty-seven consecutive GD patients with nodular goiter were included in this study (21 women and six men, mean age 41.2 years, range 22-77 years). All underwent thyroid ultrasonography and fine-needle aspiration cytology. Of the 27 patients eight underwent surgical intervention because papillary thyroid carcinoma or follicular neoplasm was diagnosed by cytology; five of these were shown to have papillary thyroid carcinomas. Ultrasonography revealed the malignant nodules to be hypoechogenic, heterogeneous, and with ill-defined margins in four of these five thyroid cancers, whereas the remaining sonogram showed a cystic change and cauliflower-like tumor formation with microcalcification. The volume and maximal diameter of cancerous nodules were significantly larger than those of benign nodules. In conclusion our results reveal that ultrasonography and fine-needle aspiration cytology are reliable and quick methods for diagnosing nodular goiters in GD patients. If thyroid neoplasms are found ablative therapy with thyroidectomy is indicated instead of radioactive iodine.

Cancer metastasizing to the thyroid is not uncommon. Prompt diagnosis and aggressive treatment appear to contribute to better prognosis in some patients. The aim of this study was to determine the clinical manifestations, ultrasonographic and cytologic findings, and outcomes in patients with metastatic thyroid cancer.We retrospectively reviewed the medical records, including clinical courses, ultrasonographic and cytologic findings, and outcomes, of 14 patients with metastatic thyroid cancer.There were various primary sites of cancer in our study population, with adenocarcinoma the most common. The sonographic images in five of 12 patients who underwent sonography showed diffusely heterogeneous hypoechoic abnormalities, while the remaining seven patients had nodular lesions. The cytologic appearances of metastatic lesions in the thyroid were characteristic of the primary malignancies.Most cancer metastatic to the thyroid presented as advanced metastases of primary malignancies. The sonographic appearance alone was not the ideal discriminator, and fine needle aspiration cytology helped define the diagnosis and management strategy.

Diabetes insipidus of central origin usually results from lesions in the hypothalamic neurohypophyseal system. Lymphocytic infundibuloneurohypophysitis is an uncommon cause. Cases of lymphocytic infundibuloneurohypophysitis with thickening of the pituitary stalk and enlargement of the neurohypophysis with no hyperintense signal in the posterior pituitary have been reported. Reported cases presenting with isolated thickening of the pituitary stalk are very rare. We report three such cases, one in a nulliparous woman and the other two in men. Magnetic resonance (MR) imaging in these patients revealed isolated thickening of the pituitary stalk, loss of the hyperintense signal of the posterior pituitary, and an adenohypophysis of normal size. All cases had abnormal nodular infundibular enlargement. One male patient had hypogonadism; the other patients showed no sign of adenohypophyseal deficiency on stimulation test. Serial follow-up MR imaging revealed that all three patients had persistent thickening of the pituitary stalk. Diabetes insipidus was controlled by the administration of desmopressin acetate in all patients.

In rare cases, cerebellar metastasis originating in serous papillary adenocarcinoma of the ovary can mimick Ménière's disease.A 51-year-old woman, with complete remission after optimal maximal debulking and chemotherapy for an International Federation of Gynecology and Obstetrics IIIc primary ovarian carcinoma, presented with nausea, vomiting, vertigo and headache 18 months after surgery. Investigations revealed a solitary cerebellar cystic mass, 4.6 x 4.0 x 3.2 cm. Gross total excision of the cerebellar lesion followed by brain irradiation resulted in complete resolution of her symptoms. Histology showed a metastatic tumor consistent with the primary ovarian carcinoma.In an atypical presentation in patients with metastatic ovarian carcinoma, thorough investigations should be done to rule out or confirm brain metastasis, which can be aggressively managed to prevent serious consequences and improve outcome.

To evaluate the histologic nature of low grade intraepithelial lesion (LSIL) in a region with a high prevalence of invasive cervical carcinoma and to propose a management protocol.Comparing the follow-up of 877 women with LSIL during a 43-month period, taking into consideration the histologic nature determined by colposcopic biopsy, endocervical curettage, conization or hysterectomy as the final pathologic diagnosis.During the study period, from July 1994 to February 1998, a total of 128,925 Pap smears were performed at our institute, with 877 (0.68%) diagnosed as LSIL. Among these, 722 women with CIN1-SIL and 32 with human papillomavirus-related changes (HPV-SIL) were enrolled in the study. Of the 543 women with CIN 1/squamous intraepithelial lesion, 145 (27%) cases of high grade squamous intraepithelial lesion were disclosed histologically, as were 16 (3%) cases of microinvasion. Among those followed at an interval of three months with a Pap smear alone, the persistence rate was 46.8%, while the regression rate was 40%. Thirty-two women with HPV/SIL underwent histologic evaluation, revealing 18% CIN 2/3 with no microinvasion.A high percentage of CIN 2/3 as well as microinvasive lesions will go unnoticed in the absence of colposcopic evaluation.

To assess the results of and factors associated with the outcome of surgery for acromegaly.We retrospectively examined the medical records of acromegalic patients who underwent trans-sphenoidal adenomectomy at our hospital during the period of January 1991 through August 1997. Preoperative evaluations included measurement of basal serum growth hormone (GH), insulin-like growth factor-I (IGF-I), prolactin (PRL), GH response to oral glucose, and GH and PRL response to bromocriptine, as well as pituitary magnetic resonance (MR) imaging. Postoperative evaluations included measurement of basal serum GH and IGF-I concentrations, and pituitary MR imaging.Thirty patients (14 men) with a mean age of 38 years were included. The mean follow-up period was 50 months (range, 15-90 mo). Ten of the 30 patients (33%) had early postoperative (1 mo after surgery) GH levels of less than 5 ng/mL. Twenty patients (67%) had final postoperative (last follow-up, 15-90 mo after surgery) GH levels of less than 5 ng/mL. Preoperative GH levels were positively correlated with early postoperative GH levels (r = 0.458, p = 0.011) and final postoperative GH levels (r = 0.479, p = 0.007). Early postoperative GH levels were also positively correlated with final postoperative GH levels (r = 0.595, p = 0.001). Tumor grade and stage were not significantly correlated with early or final postoperative GH levels. Thirteen of 21 patients (62%) who had postoperative MR imaging follow-up had residual tumor. There was no surgical mortality.These results highlight that acromegaly is not easily treated with surgery alone. The preoperative GH level was associated with the surgical outcome.

The effect of retinoic acid and dexamethasone on alkaline phosphatase (AP) expression was investigated in human breast cancer MCF-7 cells. Cellular AP activity was induced significantly by retinoic acid or dexamethasone in a time-dependent and dose-dependent fashion. A marked synergistic induction of AP activity was observed when the cells were incubated with both agents simultaneously. Two AP isozymes, tissue-nonspecific (TNAP) and intestinal (IAP), were shown to be expressed in MCF-7 cells as confirmed by the differential rate of thermal inactivation of these isozymes and RT-PCR. Based on the two-isozyme thermal-inactivation model, the specific activities for TNAP and IAP in each sample were analyzed. TNAP activity was induced only by retinoic acid and IAP activity was induced only by dexamethasone. Whereas dexamethasone conferred no significant effect on TNAP activity, retinoic acid was shown to inhibit IAP activity by approximately 50%. Interestingly, TNAP was found to be the only isozyme activity superinduced when the cells were costimulated with retinoic acid and dexamethasone. Northern blot and RT-PCR analysis were then used to demonstrate that the steady-state TNAP mRNA level was also superinduced, which indicates that the superinduction is regulated at the transcriptional or post-transcriptional levels. In the presence of the glucocorticoid receptor antagonist RU486, the dexamethasone-mediated induction of IAP activity was blocked completely as expected. However, the ability of RU486 to antagonize the action of glucocorticoid was greatly compromised in dexamethasone-mediated superinduction of TNAP activity. Furthermore, in the presence of retinoic acid, RU486 behaved as an agonist, and conferred superinduction of TNAP gene expression in the same way as dexamethasone. Taken together, these observations suggest that the induction of IAP activity by dexamethasone and the superinduction of TNAP by dexamethasone were mediated through distinct regulatory pathways. In addition, retinoic acid plays an essential role in the superinduction of TNAP gene expression by enabling dexamethasone to exert its agonist activity, which otherwise has no effect.

This study was designed to determine whether screening for high-risk human papillomaviruses testing could improve the detection of cervical dysplasia and cancer in assistance with conventional Papanicoloau (Pap) smears.The study was based on 114 patients with abnormal Pap smears referred for colposcopy from Feb. 1997 to Dec. 1997. The presence of high-risk human papillomavirus (HPV) DNA was determined with the Hybrid Capture method (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Cytologic examination by Papanicolaou smear was based on the Bethesda system and cervical biopsy was done via colposcopy.Cytologic examination demonstrated high-grade squamous intraepithelial lesions (HSIL) in 24 patients with HPV positive (75%), low-grade squamous intraepithelial lesions (LSIL) in 38 with 61% HPV positive, and atypical squamous cells of undetermined significance (ASCUS) in 52 with 37% HPV positive. Among patients with a cytologic diagnosis of borderline abnormalities (ASCUS or LSIL), those with who were HPV positive were significantly more likely to have cervical dysplasia (both p0.05). The sensitivity of combined HPV assay and/or cytology for detection of noninvasive precursor (91%) was significantly greater than those of cytology (68%) or HPV assay (81%) alone.The addition of the hybrid capture high-risk HPV DNA assay to cytologic examination of cervical smears appears to increase the sensitivity of cervical screening. Our findings suggest that HPV DNA may be a useful adjunct marker for early detection of cervical dysplasia in women with minimally abnormal Pap smears (ASCUS/low-grade SIL).

We report a case of multiple endocrine neoplasia type 2B (MEN 2B) with de novo RET proto-oncogene mutation. The patient, a 23-year-old Taiwanese woman, was admitted for treatment of recurrent medullary thyroid cancer (MTC) 7 years after a total thyroidectomy. Mucosal neuromas and marfanoid appearance were also noted. Because MEN 2B was suspected, the patient and her family members underwent genetic analysis. A heterozygous germline mutation at codon 918 (ATG--ACG) of the proto-oncogene RET was detected in the patient. This mutation was considered de novo, as it was not detected in either of her parents or her siblings. The patient underwent surgery for removal of the recurrent tumor. Although no pheochromocytoma was noted, regular follow-up is necessary because of persistent hypercalcitoninemia.

We examined the usefulness of color Doppler ultrasonography combined with ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative localization of parathyroid lesions in patients with hyperparathyroidism. Twenty-eight patients (19 men, 9 women; mean age, 56 years) with clinical and laboratory evidence of hyperparathyroidism underwent preoperative color Doppler ultrasonography and ultrasound-guided FNAC prior to surgery. On ultrasonography, the parathyroid lesions were anechoic or hypoechoic, located behind or at the margin of the thyroid gland, and mimicked blood vessels in some cases. On color Doppler ultrasound, parathyroid lesions showed little or no vascularity. They were easily differentiated from blood vessels, thus improving the safety of ultrasound-guided FNAC. Thirty-four (76%) of 45 surgically confirmed parathyroid lesions were detected with ultrasonography in 21 (75%) of the patients. There was no significant difference in the detection rates of lesions in the right upper, right lower, left upper, and left lower parathyroid glands. Eight (29%) patients had coexisting thyroid lesions. FNAC of the ultrasound-detected abnormalities provided preoperative confirmation that they were parathyroid lesions. In conclusion, our findings show that color Doppler ultrasonogrphy in combination with ultrasound-guided FNAC is useful for preoperative localization of parathyroid lesions.

The purpose of this study was to investigate pretreatment variables that could predict prognosis and to evaluate the impact of postoperative adjuvant therapy on the outcomes of patients with Stage IB or II cervical carcinoma with or without pelvic lymph node metastases.Eight hundred ninety-one patients with Stage IB or II cervical carcinoma who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment at a single institution were analyzed. Potential prognostic variables were studied.Among the variables that could be assessed before treatment, depth of cervical stromal invasion (determined by magnetic resonance imaging), clinical stage, tumor size, grade of differentiation, and DNA index (determined by flow cytometry) were independent predictors of outcome in multivariate analysis using a Cox regression model. Three distinct prognostic groups (low, intermediate, and high risk) were defined using these variables. Five-year recurrence free survival (RFS) rates for the low, intermediate, and high risk groups were 94.6%, 82.7%, and 62.3%, respectively (P = 0.0001), and overall survival (OS) rates were 98.4%, 84.5%, and 68.7%, respectively (P = 0.0001). Among patients with pelvic lymph node metastases who were free of parametrial extension, those who received postoperative chemotherapy or chemoradiotherapy had significantly better RFS (P = 0.017) and OS (P = 0.043) than those who received no adjuvant therapy. Among patients without pelvic lymph node metastases but at high risk of recurrence, those who received adjuvant radiotherapy had significantly better RFS (P = 0.015) and marginally improved OS (P = 0.087) compared with those who received no adjuvant therapy.A model containing assessable pretreatment variables for predicting the prognoses of patients with early stage cervical carcinoma was formulated. Subsets of patients for whom postoperative chemotherapy or radiotherapy might be beneficial were identified. The data from this retrospective review may be useful when future prospective trials of the treatment of early stage cervical carcinoma are designed.

Patients with malignant lesions of the adrenal gland may present with a syndrome of excess mineralocorticoids. Both primary hyperaldosteronism and excess mineralocorticoids other than aldosterone resulting from adrenal carcinoma have rarely been reported. In most patients with adrenal tumors secreting mineralocorticoids other than aldosterone, distant metastasis had already occurred at the time of diagnosis and the prognosis was poor. We present a rare case of adrenal cancer with hypertension in a patient with low plasma renin activity and a low plasma aldosterone concentration. The patient's blood pressure returned to normal after removal of the tumor. The patient is still alive and without recurrence 6 years after surgery. This case illustrates the value of thorough evaluation of hypertension and prompt surgical treatment for patients with adrenal cancer.

Thyrotropin (TSH)-secreting pituitary adenoma (TSPA) is a rare cause of hyperthyroidism and detailed reports of this entity in Taiwan are uncommon. We report a patient with TSPA with symptoms of hyperthyroidism and describe the presentation, endocrine and histologic findings, and treatment. The patient, a 42-year-old man, presented with a 2-year history of weight loss, palpitation, anxiety, and bad temper. He had increased basal serum thyroxine (T4, 18.3 micrograms/dL) and triiodothyronine (T3, 250 ng/dL) concentrations. The TSH concentration was normal (4.6 microIU/mL) and showed impaired response to stimulation by TSH-releasing hormone. Tests for antithyroid antibodies were negative. Thyroid scintigraphy showed mild thyroid enlargement. The thyroid uptake of radioactive iodine (131I) was high at 2 hours (34%) and 24 hours (63%) after 131I administration. Other serum hormone concentrations were within normal limits. Magnetic resonance imaging of the brain showed a microadenoma in the pituitary region. Octreotide and bromocriptine tests showed 78.4% and 58.3% inhibition of TSH, respectively. The patient underwent trans-sphenoidal pituitary tumor excision, and the symptoms of hyperthyroidism subsided after surgery. Six months after the operation, there was no evidence of recurrence of the tumor or symptoms of hyperthyroidism. Hormonal supplements were also not necessary. In conclusion, TSPA is a rare cause of hyperthyroidism. However, in patients with symptoms of hyperthyroidism and increased basal serum T1 and T3 concentrations, but normal or even elevated serum TSH concentrations, TSPA should be considered in the differential diagnosis.

Lymph node metastasis is established as a poor prognostic factor in cervical carcinoma patients undergoing primary surgery. However the optimal postoperative therapy for node-positive patients remains to be defined.To determine the role of adjuvant therapy in stage Ib-IIa cervical carcinoma patients who had pelvic node metastases after radical hysterectomy, a single institutional randomized controlled trial with factorial design, comparing concurrent chemo-radiotherapy (CT + RT) versus chemotherapy (CT) or radiotherapy (RT) alone was conducted. Study endpoints included site of recurrence, time to recurrence, relapse-free and overall survivals, and toxicity of treatment.At a median follow-up of 61 months, the 6-year relapse-free and overall survival rates of the 39 patients entered into this trial were 78.2% and 85.2%, respectively. This trial was prematurely closed due to suboptimal accrual and protocol violation. It is inconclusive regarding the efficacy of CT because of the limitation of the sample size and the imbalance of prognostic features by actual treatment. A model for risk group classification of patients with stage Ib-II cervical carcinoma with pelvic node metastases from a retrospective analysis was validated by this prospective cohort. The results of this failed trial suggest that adjuvant CT alone seemed comparable to RT alone or CT + RT in survival but was associated with significantly less morbidity.It is warranted to consider a CT alone arm in comparison with either observation or CT + RT according to risk of recurrence in future prospective trials. However, this important issue can only be addressed by a large multicenter trial.

The experience of the surgeon and precise localization of abnormal parathyroid glands determine the success of surgery for primary hyperparathyroidism (HPT). In HPT patients undergoing repeat surgery, the use of localization studies improved the ability to identify the remaining abnormal parathyroid tissue. This study investigated the roles of preoperative localization techniques for initial surgery for primary HPT. From 1985 through 1997, two noninvasive localization procedures, ultrasonography (US) and 201thallium chloride-99mtechnetium pertechnetate subtraction scanning (Tl-Tc), were used prior to initial exploration for primary HPT in 76 patients. Their accuracy was determined on the basis of surgical and pathologic results. The surgical success rate was 96% (73/76). The sensitivities of US and Tl-Tc were 71% and 49%, respectively. The sensitivity of Tl-Tc was higher for the lower parathyroid glands. In 21 of 26 patients who underwent fine-needle aspiration (FNA) of the suspected enlarged parathyroid gland, the diagnosis of parathyroid adenoma was confirmed preoperatively. We conclude that the concomitant use of US and FNA is a safe and convenient method for preoperative localization of the parathyroid glands prior to initial surgical exploration in patients with primary HPT. Bilateral neck exploration by an experienced surgeon should be the routine procedure. US and Tl-Tc alone offer limited localization information, and unilateral exploration should be reserved for selected cases in which the results of these two imaging studies are consistent with one another.

We evaluated the effectiveness of slow-release lanreotide, a long-acting somatostatin analogue, in the treatment of acromegaly. Eleven patients with acromegaly were recruited, six of whom had received long-term treatment with octreotide. Lanreotide 30 mg was administered by intramuscular injection every other week for 24 weeks. The frequency of injection was adjusted as clinically needed after 2 weeks. Clinical effects were evaluated, and symptoms were recorded and scored. Finger circumferences and hand volumes were measured. Serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations were determined, and an oral glucose test was done at baseline and after treatment. Symptom scores, circumferences of the fingers, hand volumes, and serum GH and IGF-1 concentrations significantly decreased during treatment. Serum GH concentrations returned to normal in five (46%) of the 11 patients, while serum IGF-1 concentrations returned to normal in three (27%). Glucose intolerance was not significantly improved at the end of treatment. Although the mean serum GH concentration was significantly decreased after treatment, it was still not suppressed by glucose. In conclusion, slow-release lanreotide, given either twice or three times a month, is effective in controlling acromegalic symptoms as well as GH and IGF-1 hypersecretion. The treatment is well tolerated and convenient for patients.

To elucidate the germline RET proto-oncogene mutations in Taiwanese families with multiple endocrine neoplasia type 2A (MEN 2A), we extracted DNA from peripheral blood leukocytes of 28 members of two families with MEN 2A. Oligonucleotide primers for exons 10 and 11 were used to analyze the nucleotide sequence of codons 609, 611, 618, and 620 of exon 10, and codon 634 of exon 11 of the RET proto-oncogene. Two fragments of genomic DNA were amplified by polymerase chain reaction (PCR). The amplified PCR products were separated and purified from primers and free nucleotides in agarose gels, and the expected 187-bp and 234-bp bands were cut from the gels and sequenced. Thirteen family members in the two MEN 2A kindreds had mutations in codon 634 of exon 11. In kindred 1 (15 members available for this study), a heterozygous codon 634 mutation in nine members and a homozygous codon 634 mutation in one member led to the substitution of Phe (TTC) for Cys (TGC). Three members of kindred 2 (13 members available for this study) had a heterozygous base pair change in codon 634, which led to the substitution of Arg (CGC) for Cys (TGC). In this study, we found two mutation events occurring in two MEN 2A kindreds and also discovered a homozygous point mutation in one woman that led to heterozygous mutations in all of her children.

We examined RET protooncogene mutations in sporadic medullary thyroid carcinoma (MTC), using polymerase chain reaction (PCR)-based sequencing. DNA was extracted from tumor tissue and peripheral blood leukocytes of seven unrelated individuals with apparently sporadic MTC. Oligonucleotide primers were selected to amplify exons 10, 11, 13, 15, and 16 of the RET protooncogene, to examine the sequences of codons 609, 611, 618, and 620 of exon 10, codon 634 of exon 11, codon 768 of exon 13, codon 883 of exon 15, and codon 918 of exon 16. Direct DNA sequencing from PCR products was then performed. The results showed that one patient had a somatic mutation at codon 918 (ATG--ACG), causing a Met--Thr substitution. One patient had a de novo germline mutation at codon 634 (TGC--CGC), causing a Cys--Arg substitution. Another patient had a germline mutation at codon 634 (TGC--TTC), causing a Cys--Phe substitution. In the remaining four cases, no RET mutations were found. Unexpectedly, two offspring of the patient (a female) with a germline mutation at codon 634 (TGC--TTC) harbored homozygous alleles for the mutation; because the father did not carry this mutation, the other affected allele was suspected to have resulted from a de novo germline mutation of paternal origin. One of these offspring was subsequently diagnosed as having MTC. Our findings suggest that all patients with apparently sporadic MTC should be screened for the RET protooncogene by molecular analysis to detect occult or de novo multiple endocrine neoplasia 2 (MEN 2) or familial MTC. This would allow early treatment of affected family members.