Incorporating blood-based liquid biopsy information into cancer staging: time for a TNMB system?

Tissue biopsy is the standard diagnostic procedure for cancer. Biopsy may also provide material for genotyping, which can assist in the diagnosis and selection of targeted therapies but may fall short in cases of inadequate sampling, particularly from highly heterogeneous tumors. Traditional tissue biopsy suffers greater limitations in its prognostic capability over the course of disease, most obviously as an invasive procedure with potential complications, but also with respect to probable tumor clonal evolution and metastasis over time from initial biopsy evaluation. Recent work highlights circulating tumor DNA (ctDNA) present in the blood as a supplemental, or perhaps an alternative, source of DNA to identify the clinically relevant cancer mutational landscape. Indeed, this noninvasive approach may facilitate repeated monitoring of disease progression and treatment response, serving as a means to guide targeted therapies based on detected actionable mutations in patients with advanced or metastatic solid tumors. Notably, ctDNA is heralding a revolution in the range of genomic profiling and molecular mechanisms to be utilized in the battle against cancer. This review will discuss the biology of ctDNA, current methods of detection and potential applications of this information in tumor diagnosis, treatment, and disease prognosis. Conventional classification of tumors to describe cancer stage follow the TNM notation system, heavily weighting local tumor extent (T), lymph node invasion (N), and detectable metastasis (M). With recent advancements in genomics and bioinformatics, it is conceivable that routine analysis of ctDNA from liquid biopsy (B) may make cancer diagnosis, treatment, and prognosis more accurate for individual patients. We put forward the futuristic concept of TNMB tumor classification, opening a new horizon for precision medicine with the hope of creating better outcomes for cancer patients.

Incorporation of log odds of positive lymph nodes into the AJCC TNM classification improves prediction of survival in oral cancer.

OBJECTIVES: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients. DESIGN: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic. SETTING: Medical centrer in Taiwan. PARTICIPANTS: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC. MAIN OUTCOME MEASURES: The discriminability for 5-year DSS rates. RESULTS: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764). CONCLUSIONS: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy.

The impact of smoking on incident type 2 diabetes in a cohort with hepatitis B but not hepatitis C infection.

Smoking may be a risk factor for diabetes, and it has been suggested that viral hepatitis may predispose to diabetes. We studied diabetes and smoking histories in people with viral hepatitis. From 1997 to 2004, we studied the risk of incident diabetes in a community cohort with hyperendemic HBV and HCV infection in southern Taiwan. The cohort involved 3539 people (40-70 years old) without diabetes. Four hundred and twenty-three individuals developed diabetes. Those who were ≥65 years old, frequently consumed alcohol, had a BMI ≥25, had <9 years of education, were anti-HCV+ or smoked ≥1 pack per day were more likely to develop diabetes (P < 0.05). A cumulative hazard function test showed that the higher the smoking levels, the greater the cumulative incidence rate of diabetes in HBsAg+ participants only (P = 0.03 by log-rank test). A multiple Cox proportional hazards model analysis in different hepatitis statuses showed smoking levels were strong predictors of diabetes with a dose-response relationship for type 2 diabetes in those with HBsAg+ : hazard ratio (HR) = 3.8, (95% CI: 1.2, 12.3) for light smokers (<1 pack per day) and HR = 4.4 (95% CI: 1.5, 13.3) for heavy smokers (≥1 pack per day). Increasing BMI was a common predictor in all people. Smoking is a strong predictor for diabetes with a dose-response relationship in HBsAg+ individuals and a mild predictor for seronegative individuals but not significant in anti-HCV+ individuals.

Anterior debridement may not be necessary in the treatment of tuberculous spondylitis of the thoracic and lumbar spine in adults: a retrospective study.

AIM: Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients. PATIENTS AND METHODS: Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit. RESULTS: The mean kyphotic angle improved from 26.1° (- 1.8° to 62°) to 15.2° (-25° to 51°) immediately after the operation. At a mean follow-up of 68.8 months (30 to 144) the mean kyphotic angle was 16.9° (-22° to 54°), with a mean loss of correction of 1.6° (0° to 10°). There was a mean improvement in neurological status of 1.2 Frankel grades in those with a neurological deficit. Bony union was achieved in all patients, without recurrent infection. CONCLUSIONS: Long posterior instrumentation with short posterior or posterolateral fusion is effective in the treatment of TB spine. It controls infection, corrects the kyphosis, and maintains correction and neurological improvement over time. TAKE HOME MESSAGE: With effective anti-TB chemotherapy, a posterior only procedure without debridement of anterior lesion is effective in the treatment of TB spondylitis, and an anterior procedure can be reserved for those patients who have not improved after posterior surgery. Cite this article: Bone Joint J 2016;98-B:834-9.

Omental mesenteric myxoid hamartoma, a subtype of inflammatory myofibroblastic tumor? Considerations based on the histopathological evaluation of four cases.

Omental mesenteric myxoid hamartoma (OMH) is a distinctive myxoid lesion of infancy, characterized by a benign clinical behavior. In the current World Health Organization (WHO) classification of soft tissue tumors, it is considered as part of the morphologic spectrum of inflammatory myofibroblastic tumors (IMT), but this relationship with IMT is still subject to debate. Four lesions with histologic features of OMH occurring in newborns and toddlers are described and compared with classic, ALK-positive IMT. All OMH showed a peculiar dot-like immunostaining for ALK, which, in one of the cases, was cytogenetically found to be associated with an inversion of the ALK gene. While OMHs were positive for smooth muscle actin (SMA), desmin, WT1, podoplanin, and cytokeratins (CAM5.2 and AE1-3), IMT were consistently positive only for SMA (10 cases). ALK-1 displayed cytoplasmic staining in IMT and characteristic paranuclear dot-like staining in OMH.

Factors correlated with tuberculosis reported after death.

SETTING: Taiwan. OBJECTIVE: To determine factors associated with tuberculosis (TB) reported after death. DESIGN: A retrospective cohort study was conducted of TB patients newly registered between 2006 and 2008. The national TB database was linked with the Vital Registry System and National Health Insurance database for analysis. RESULTS: A total of 1409 (4.0%) TB cases were reported after death. Age ⩾75 years (OR 1.70), chest X-ray (CXR) unknown or not performed (OR 2.41), positive sputum bacteriology (OR 1.74), and comorbidities such as cancer (OR 1.21), chronic liver disease (OR 1.21) and chronic kidney disease (OR 2.58) were associated with the reporting of TB cases after death. More than 30% of TB deaths in elderly persons with chronic kidney disease were TB cases that were reported after death. Abnormal CXR and comorbidities such as chronic obstructive pulmonary disease, stroke and diabetes mellitus were less likely to be associated with the reporting of TB cases after death. CONCLUSIONS: Elderly patients with cancer, chronic liver disease or chronic kidney disease require more attention to prevent delayed diagnosis and early mortality from TB. Elderly patients with chronic kidney disease are at highest risk.

Smoking increases risk of recurrence after successful anti-tuberculosis treatment: a population-based study.

OBJECTIVE: To investigate whether tobacco smoking increases the risk of tuberculosis (TB) recurrence and identify factors associated with TB recurrence among adults who had successfully completed anti-tuberculosis treatment in Taipei, Taiwan. METHODS: Recurrence was defined as a new clinical or microbiological diagnosis of TB requiring the start of a new course of treatment in a patient who had satisfactorily completed treatment for a previous TB episode. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) for recurrence. RESULTS: We followed 5567 adults for recurrence after successful anti-tuberculosis treatment. The mean age was 58.5 years; 62.9% were male. Overall, 84 (1.5%) had a recurrence of TB during follow-up. The incidence of TB recurrence was 4.9 episodes/1000 person-years of follow-up. Cox proportional hazards regression showed that after controlling for other variables, the risk of TB recurrence among subjects who smoked >10 cigarettes a day was double that of never/former smokers. Other independent risk factors significantly associated with TB recurrence were homelessness (aHR 3.75, 95%CI 1.17-12.07), presence of comorbidities (aHR 2.66, 95%CI 1.22-5.79) and a positive acid-fast bacilli smear (aHR 2.27, 95%CI 1.47-3.49). CONCLUSION: Smoking >10 cigarettes a day was significantly associated with TB recurrence. To reduce the risk of recurrence, we recommend including effective measures of smoking cessation in TB control programmes, as recommended by the World Health Organization Stop TB Strategy.

Prescription of atropine eye drops among children diagnosed with myopia in Taiwan from 2000 to 2007: a nationwide study.

PURPOSE: This study was conducted to examine the atropine eye drop prescription trend for children diagnosed with myopia, and to determine the factors associated with the prescription of atropine eye drops. DESIGN: This was a population-based cross-sectional study. METHODS: This study was conducted using a national representative sample from the National Health Insurance (NHI) claims data. All school children between 4 and 18 years of age who had visited an ophthalmologist and were diagnosed with myopia between 2000 and 2007 were included herein. The main outcome measure was the proportion of subjects who were prescribed atropine eye drops in each year. Logistic regression was used to identify the factors associated with atropine eye drops being prescribed. RESULTS: The prescription of atropine eye drops for children diagnosed with myopia increased significantly from the school years 2000 (36.9%) to 2007 (49.5%). There was also a shift from prescribing high concentrations (0.5 and 1%) of atropine eye drops to lower concentration ones (0.3, 0.25, and 0.1%) within this period. Atropine eye drops were more frequently prescribed to 9-12-year-old children (OR=1.26-1.42, compared with those 7-8 years old), and to children from families with a high socioeconomic status (OR=1.19-1.25); however, they were less prescribed to those living in mid to low urbanized areas (OR=0.65-0.84). CONCLUSIONS: This study revealed an increasing trend of atropine eye drop prescription for children with myopia in Taiwan. Our study provides eye-care professionals worldwide a reference for the potential integration of atropine eye drops into their clinical practice toward children with myopia.

Increased stroke risk in Bell's palsy patients without steroid treatment.

BACKGROUND AND PURPOSE: To investigate the risk of stroke development following a diagnosis of Bell's palsy in a nationwide follow-up study. METHODS AND MATERIALS: Information on Bell's palsy and other factors relevant for stroke was obtained for 433218 eligible subjects without previous stroke who had ambulatory visit in 2004. Of those, 897 patients with Bell's palsy were identified. Over a median 2.9 years of follow-up, 4581 incident strokes were identified. We estimated hazard ratios (HR) and 95% confidence intervals [CI] with Cox proportional hazard models adjusting for age, sex, co-morbidities, and important risk factors. Standardized incidence ratio of stroke amongst patients with Bell's palsy was analyzed. RESULTS: Compared with non-Bell's palsy patients, patients with Bell's palsy had a 2.02-times (95% CI, 1.42-2.86) higher risk of stroke. The adjusted HR of developing stroke for patients with Bell's palsy treated with and without systemic steroid were 1.67 (95% CI, 0.69-4) and 2.10 (95%, 1.40-3.07), respectively. CONCLUSIONS: Patients with Bell's palsy carry a higher risk of stroke than the general population. Our data suggest that these patients might benefit from a more intensive stroke prevention therapy and regular follow-up after initial diagnosis.

Nucleic acid amplification test and bronchoscopy improve the diagnostic accuracy of smear-negative tuberculosis.

OBJECTIVE: To determine whether the nucleic acid amplification (NAA) test on specimens collected by bronchoscopy improves the diagnostic accuracy of pulmonary tuberculosis (PTB) in sputum-negative patients. DESIGN: Bronchoscopy was performed among smear-negative PTB suspects to collect respiratory specimens to assess the efficacy and accuracy of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test in the diagnosis of PTB. RESULTS: In 105 PTB suspects, 80 were finally excluded, of whom two were false-AMTD-positive. PTB (n = 25) was diagnosed in 10 patients culture-positive for Mycobacterium Tuberculosis (7/105 bronchial wash/bronchoalveolar lavage [BW/BAL] specimens, 6/315 expectorated sputum specimens [2 positive in 2 patients; 1 positive in 2 patients], and one with both), and in 15 patients with improvement after anti-tuberculosis treatment. Among the 25 PTB patients, 20 were AMTD-positive, of whom four were culture-positive. Three AMTD-negative patients were culture-positive. The sensitivity and specificity of AMTD were respectively 80.0% and 97.5%. The diagnostic yield was higher in respiratory specimens obtained at bronchoscopy and measured by AMTD than in conventional sputum or BW/BAL culture. CONCLUSION: NAA testing on specimens collected using bronchoscopy provides a highly efficient and reliable approach in the diagnosis of PTB in smear-negative PTB suspects.

TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death.

Self-aggregation of transforming growth factor ß (TGF-ß)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid ß (Aß) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aß in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aß aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aß. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aß formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage-independent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death.

COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3σ.

14-3-3σ, a gene upregulated by p53 in response to DNA damage, exists as part of a positive-feedback loop, which activates p53 and is a human cancer epithelial marker downregulated in various cancer types. 14-3-3σ levels are critical for maintaining p53 activity in response to DNA damage and regulating signal mediators such as Akt. In this study, we identify mammalian constitutive photomorphogenic 1 (COP1) as a novel E3 ubiquitin ligase for targeting 14-3-3σ through proteasomal degradation. We show for the first time that COP9 signalosome subunit 6 (CSN6) associates with COP1 and is involved in 14-3-3σ ubiquitin-mediated degradation. Mechanistic studies show that CSN6 expression leads to stabilization of COP1 through reducing COP1 self-ubiquitination and decelerating COP1's turnover rate. We also show that CSN6-mediated 14-3-3σ ubiquitination is compromised when COP1 is knocked down. Thus, CSN6 mediates 14-3-3σ ubiquitination through enhancing COP1 stability. Subsequently, we show that CSN6 causes 14-3-3σ downregulation, thereby activating Akt and promoting cell survival. Also, CSN6 overexpression leads to increased cell growth, transformation and promotes tumorigenicity. Significantly, 14-3-3σ expression can correct the abnormalities mediated by CSN6 expression. These data suggest that the CSN6-COP1 axis is involved in 14-3-3σ degradation, and that deregulation of this axis will promote cell growth and tumorigenicity.

Treatment and survival in breast cancer in the Eastern Region of England.

BACKGROUND: The reasons for variation in survival in breast cancer are multifactorial. METHODS: From 1999 to 2003, the vital status of 9051 cases of invasive breast cancer was identified in the Eastern Region of England. Survival analysis was by Cox proportional hazards regression. Data were analysed separately for patients aged <70 years and those older due to differences in treatment policies. RESULTS: Overall 5-year survival was 78%. In patients aged <70 years, significant differences in survival lost their formal significance after adjustment for detection mode and node status, although this remained close to statistical significance with some residual differences between relative hazards. There was significant negative ecological correlation between proportion with nodes positive or not examined and 9-year survival rates. Patients with estrogen receptor (ER) status unknown were at significantly higher risk of dying than ER-positive patients. There was a clear trend of increasing hazard of dying with increasing deprivation. Survival differences in women aged > or =70 years were related to whether surgery was included as part of treatment. CONCLUSION: This variation in treatment and survival may be attributed to lack of information, in particular nodal and ER status, thereby impacting on staging and prescription of adjuvant therapy.

Bidimensional measurement of nasopharyngeal carcinoma: a simple method to predict outcomes.

OBJECTIVES: To determine whether the standard techniques of measuring tumour size could be applied to the measurement of nasopharyngeal carcinoma. STUDY DESIGN: A retrospective review of case notes from the Buddhist Tzu Chi Dalin General Hospital archives was performed. SETTINGS: The Buddhist Tzu Chi Dalin General Hospital is a teaching hospital in Taiwan. PARTICIPANTS: All patients with nasopharyngeal carcinoma were included. MAIN OUTCOME MEASURES: Ninety-eight patients with newly diagnosed nasopharyngeal carcinoma were treated with high-dose radiotherapy and chemotherapy were enrolled in this study. Computed tomography-derived primary tumour volume, bidimensional measurement and unidimensional measurement were recorded. Intrarater reliability was measured. To examine the validity of various measurements, we estimated the Spearman's correlation co-efficients between those measurements and the gold standard value (primary tumour volume measurement with summation of area techniques). Univariate and multivariate analyses were performed and Kaplan-Meier survival curves constructed. RESULTS: There was a significant association between primary tumour volume and bidimensional measurement with respect to tumour size at diagnosis (Spearman's correlation co-efficient = 0.845, P < 0.001). Using age, gender, chemotherapy status and T-stage as covariate, bidimensional measurement remained an independent prognostic factor for any relapse [Hazard ratio = (HR) 1.066; P = 0.029], and overall survival (HR = 1.097; P = 0.007). Patients with small bidimensional measurement (<10 cm(2)) had better prognosis and fewer recurrences. CONCLUSIONS: When using simple measurement to evaluate nasopharyngeal carcinoma, the bidimensional measurement may be used to measure size at diagnosis. Patients with small bidimensional measurement had better prognosis and fewer recurrences. Bidimensional measurement may be further considered to improve the current staging system.

The prognostic influence of prevertebral space involvement in nasopharyngeal carcinoma.

OBJECTIVES: The purpose of this study was to evaluate the effect of prevetebral space involvement on treatment outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with radiotherapy/concurrent chemoradiotherpy or concurrent chemoradiotherpy with adjuvant chemotherapy. DESIGN: A retrospective review of case notes from the Kaohsiung Veterans General Hospital archives was performed. SETTING: A medical centre in Taiwan. PARTICIPANTS: There were 145 newly diagnosed cases of NPC. Thirty-nine patients were excluded because of the presence of distant metastasis at the time of presentation, loss of follow-up and incomplete image information. MAIN OUTCOME MEASURES: Pearson's chi-square tests were used to analyse correlation between tumour invasion and prevetebral space involvement during univariate analysis and logistic regression was applied during multivariate analysis. Kaplan-Meier survival curves were constructed. Multivariate analysis was performed to examine the impact of various prognostic factors. Pearson's chi-square and Fisher's exact test were also used to evaluate the correlation between failure patterns and treatment modality. RESULTS: A total of 106 patients with newly diagnosed NPC were enrolled in this study. Forty-three patients (41%) in this series were found to have prevertebral space involvement. Patients with prevertebral space involvement conferred a poor overall survival rate and metastasis-free survival rate compared with those without prevertebral space invasion (P = 0.04 and 0.02 respectively). Multivariate analysis showed that prevertebral space invasion was associated with an increased risk for distant metastasis [hazard ratio (HR) 14, 95% confidence interval (CI) 1.0-17.4; P = 0.03)] and overall survival (HR 7, 95% CI 1.1-135; P = 0.04). In patients with prevertebral space involvement, their metastasis-free survival rate, with and without adjuvant chemotherapy, was 100% and 72.7% (P = 0.047). This phenomenon was not observed in NPC patients without prevertebral space invasion. CONCLUSIONS: The present data revealed that prevertebral space involvement has a close relationship with survival rates and recurrence rates of patients with NPC. Nasopharyngeal carcinoma patients with prevertebral space involvement have more recurrence and poorer survival rates and should be the group to benefit from concurrent chemoradiotherapy followed by adjuvant chemotherapy. Inclusion of prevertebral space involvement may be needed to predict prognosis of NPC and help us to identify the high-risk group.

Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone?

This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50-70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection compared with symptomatic diagnosis on 5-year survival unadjusted, then adjusted for age and Nottingham Prognostic Index (NPI). A total of 72% of the survival benefit associated with screen-detected breast cancer can be accounted for by age and shift in NPI. Survival analysis by continuous NPI showed a small but systematic survival benefit for screen-detected cancers at each NPI value. These data show that although most of the screen-detected survival advantage is due to a shift in NPI, the mode of detection does impact on survival in patients with equivalent NPI scores. This residual survival benefit is small but significant, and is likely to be due to differences in tumour biology. Current prognostication tools may, therefore, overestimate the benefit of systemic treatments in screen-detected cancers and lead to overtreatment of these patients.

Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post-operative adjuvant therapy.

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was <4 cm in 96 patients and > or = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was <2/3 in 20 patients and > or = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P < 0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size <4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.

The impact of the menopause on coronary artery calcification examined by multislice computed tomography scanning.

BACKGROUND AND AIMS: To examine whether there is a difference in coronary artery calcification (CAC) scores between males and females aged above 50 years. METHODS AND RESULTS: A total of 479 subjects aged between 40 and 70 years with no clinical or family history of cardiovascular disease (CVD) were enrolled for this study. All subjects were assessed by multislice CT scanning (MCTS), and the CAC scores obtained were assigned to one of four quartiles for further assessment and comparison. The main outcome evaluated was the percentage of high CAC scores and mean CAC scores, comparing males and females of different age groups. This study found that the percentage of high CAC scores increased markedly from 5% (40-49 age group) to 21.2% (50-59 age group) among females. The increase was significantly less when comparing males from different age groups (from 25% in the 40-49 age group to 31.2% in the 50-59 age group). Females had higher odds ratios (ORs) postmenopausally (4.3 in the 50-59 age group) than males in the same age group (1.6). CONCLUSIONS: These initial findings seem to indicate that above 50 years of age, CAC is more dependent on age in females than in males, which might be due to the effect of the menopause.