Stage Shift Research Articles

Method of detection is a prognostic factor for outcome among women diagnosed with early stage breast cancer.

Abstract Abstract #5005 Background: The reduction in breast cancer mortality over the past several decades has been partially attributed to the impact of screening mammograms. Breast cancers detected by screening mammograms tend to be at an earlier stage than those detected as a result of symptoms. The magnitude of the impact of method of detection on breast cancer survival beyond this phenomenon, known as stage shift, is not well defined. We therefore evaluated the independent prognostic effect of method of detection among women diagnosed in early stages of disease (stage I and II breast cancers). Methods: Medical records from 2,143 women aged 40 or older with stage I and II breast cancers, treated at the M.D. Anderson Cancer Center between 1985 and 2000 were used to derive information on method of breast cancer detection, clinical and histological tumor characteristics. Cox proportional hazards models were used to estimate the hazard ratios (HR) of breast cancer recurrence and breast cancer-specific death adjusted for age at diagnosis, year of diagnosis, nuclear grade, hormone receptor status, systemic treatment and stage at diagnosis. All statistical tests were two-sided. Results: Patients ages 40-49, 50-69 and ≥70 with symptom compared to screen-detected breast cancers were statistically significantly more likely to be diagnosed with stage II versus stage I disease and were more likely to have higher nuclear grade III versus grade I tumors. Symptom-detected breast cancers were associated with an increased risk of breast cancer recurrence (HR 1.9, 95% confidence interval (CI) 1.4-2.6) and breast cancer-specific death (HR 2.0, 95% CI 1.4-3.0) than screen-detected breast cancers after adjusting for age at diagnosis, year of diagnosis, tumor size, lymph node involvement, tumor characteristics and systemic treatment. Discussion: Our data from a large cohort of breast cancer patients with long-term follow-up indicate that even among patients with early stage disease; those with symptom-detected breast cancers have a worse prognosis. Consideration should be given to including method of detection as a prognostic factor when making treatment decisions for patients with stage I and II breast cancers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5005.

Survival Trends in Patients With Gastric and Esophageal Adenocarcinomas: A Population-Based Study

To use a population-based approach to describe survival trends in patients diagnosed as having gastric or esophageal adenocarcinoma. A population-based complete chart review of all inpatient and outpatient records, using the resources of the Rochester Epidemiology Project, was conducted in Olmsted County, Minnesota (population 124,277), a primarily rural county with one large urban area. All residents of Olmsted County who were diagnosed as having gastric or esophageal adenocarcinoma from January 1, 1971, through December 31, 2000, were included in the study. The main outcomes were median survival and 2-year and 5-year survival rates, by decade of diagnosis. From 1971 through 2000, median survival for patients with gastric adenocarcinoma (n=121) decreased from 5.5 months to 3.2 months, whereas median survival for patients with esophageal adenocarcinoma (n=65) increased from 8.5 months to 11.7 months. Decade of diagnosis was not significantly associated with patient survival for either gastric or esophageal adenocarcinoma (P>.05). There was no significant shift in stage of disease at diagnosis during the 30-year period for either gastric or esophageal adenocarcinoma (P>.05). No significant change has occurred in the survival rates of this patient population with gastric or esophageal adenocarcinoma, which is representative of the US white population.

Has the two-week straight to test protocol affected the T stage of the disease for colorectal cancer?

Introduction: The provision of services for early colorectal cancer detection has seen the introduction of the two-week straight to test protocol (STT). The efficacy of such protocols in demonstrating a T stage shift for colon cancers is not known.

Survival from prostate cancer in England and Wales up to 2001

Survival from prostate cancer in England and Wales up to 2001

NREM sleep instability changes following rapid maxillary expansion in children with obstructive apnea sleep syndrome

Objective To evaluate NREM sleep microstructure in children with obstructive sleep apnea syndrome (OSAS) before and after one year of rapid maxillary expander (RME) treatment by means of the cyclic alternating pattern (CAP). Methods Nine children with OSAS aged 4–8 years (6 males, mean age 6.4 ± 1.97 years) and age-matched normal controls were included. All subjects underwent an overnight polysomnography in the sleep laboratory after one adaptation night, as a baseline evaluation; children with OSAS were recorded again after one year of RME treatment. Results After one year of treatment the OSAS group showed a longer duration of time in bed and sleep period time, a reduction in number of stage shifts compared to baseline recordings, and the apnea–hypopnea index decreased significantly. At baseline, the OSAS group had a higher CAP rate during slow-wave sleep and an increased A2 index compared to normal controls. After one year of RME application, children with OSAS showed an increase in CAP rate associated with an increase of A1 index during slow-wave sleep. Conclusions RME treatment almost normalized sleep architecture and improved sleep respiratory disturbances; however, sleep microstructure and respiratory parameters did not completely recover. The persistence of increased CAP rate in slow-wave sleep associated with an increase of A1 index might reflect a partial failure of orthodontic treatment. On the other hand, the rebound of A1 subtypes might be an indirect sign of an attempt to normalize sleep that has been disturbed by the respiratory events.

Pulmonary tumours in the Netherlands: focus on temporal trends in histology and stage and on rare tumours

Background:Recent temporal trends in histology and stage of pulmonary tumours in the Netherlands were studied. The incidence of rare pulmonary tumours was determined.Methods:All tumours originating from the trachea, bronchus and...

The screening mammography paradox: better when found, perhaps better not to find

The screening mammography paradox: better when found, perhaps better not to find

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.

Stage shift in lung carcinogenesis, a practical reality

Stage shift in lung carcinogenesis, a practical reality

Impact of patellofemoral osteoarthritis on long-term outcome of high tibial osteotomy and effects of ventralization of tibial tubercle

BackgroundMedial compartment osteoarthritis (OA) of the knee frequently accompanies patellofemoral osteoarthritis (PF-OA). No consensus has been reached whether it is better to include treatment for the PF joint at the time of high tibial osteotomy (HTO), or if treatment of the PF joint is unnecessary. The purpose of this comparative retrospective study on medial compartment OA of the knee accompanying PF-OA was to examine the effects of PF-OA on the long-term outcome of HTO and to evaluate the significance of ventralization of the tibial tubercle when combined with HTO. MethodsWe studied the impact of PF-OA on the long-term outcome of HTO and the effects of ventralization of the tibial tubercle, which was performed in conjunction with HTO for medial and PF compartment OA more than 10 years previously. The 42 subjects included 14 men (15 knees) and 26 women (27 knees). Their mean age at the time of surgery was 60.7 years, and the follow-up period was 10–15 years (average 12 years). Ventralization of the tibial tubercle was performed on 18 knees. ResultsA significant relation was observed between improvement of the clinical knee score and preoperative radiological PF-OA stage in the HTO patients (P < 0.05). Radiologically, no correlation was observed between the shift in radiological PF-OA stage and the presence or absence of ventralization of the tibial tubercle. Among the preoperative radiological moderate and severe PF-OA cases, no significant relation was found between the presence or absence of ventralization of the tibial tubercle performed with HTO and improvement of the knee joint function score. ConclusionIn cases of severe PF-OA in which HTO was performed, ventralization of the tibial tubercle as combined surgery did not prove effective at the long-term follow-up.

Effects of Dispersed Al&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; Particles on Sintering of LTCC

The sintering of Low Temperature Co-fired Ceramics prepared from alumoborosilicate glass- and Al2O3 powders of similar small particle size was studied by dilatometry, heating microscopy, microstructure analysis, glass- and effective viscosity measurements. The steric effect of Al3O3 inclusions was studied using a “non-reactive” model composite. With increasing Al3O3 volume fraction ( Φ ≤ 0.45), sintering decelerates and its final stage shifts to higher temperature. The attainable shrinkage is reduced as Al2O3 particle clusters bearing residual pores become more frequent. The kinetics of sintering could be described formally superposing the weighed contributions of differentially sized and randomly composed glass-crystal particle clusters and assuming a sintering rate controlled by the effective matrix viscosity, which increases with Φ and with progressive wetting of Al2O3 particles during densification. The “reactive” model composite shows significant dissolution of Al2O3 into the glass, which has two opposed effects on sintering: reducing Φ and increasing glass viscosity. For the present case ( Φ = 0.25), the latter effect dominates and sintering is retarded by Al2O3 dissolution. Crystallization of wollastonite starts after full densification. Dissolution of Al2O3 was found to promote the subsequent growth of anorthite.

Sleep stage dynamics in fibromyalgia patients and controls

Objective To determine whether previously described sleep stage dynamics, reflecting the mean duration of specific sleep stages, may have clinical utility in a sample of patients with fibromyalgia syndrome (FMS) and controls. Methods Women with FMS ( n = 15, screened to exclude other sleep disorders) and age-matched women in good health ( n = 15) were studied with nocturnal polysomnography, multiple sleep latency tests, 2-week pain diaries, and a measure of current pain intensity. Results The FMS subjects, in comparison to controls, did not show differences in several common polysomnographic measures, except for increased numbers of stage shifts (126 ± 27 vs. 107 ± 22, p = .042). Mean durations for episodes of total sleep, stage 1 sleep, stage 3/4 sleep, and rapid eye movement sleep failed to distinguish FMS and control subjects (Wilcoxon rank sum tests, p > .10 for each), but those for stage 2 sleep were shorter in the FMS subjects ( p = .006), possibly because transitions to stage 3/4 sleep occurred more quickly ( p = .036). Shorter stage 2 sleep durations predicted higher pain diary scores (Spearman rho = −.56, p = .0014) and current pain intensity ( rho = −.71, p < 0.0001). Conclusions Sleep stage dynamic, and, more specifically, shorter durations of sleep stage 2 periods, distinguish FMS and control female subjects and may predict pain levels experienced in FMS. Analysis of the lengths of individual sleep stages, in addition to the usual sleep stage amounts and percentages listed in standard polysomnogram reports, may have clinical utility.

Prospective assessment of lymphatic dissemination in endometrial cancer: A paradigm shift in surgical staging

Objective To prospectively assess pelvic and para-aortic lymph node metastases in endometrial cancer with lymphatic dissemination, emphasizing the examination of para-aortic metastases relative to the inferior mesenteric artery (IMA). Methods Over 36 months, 422 consecutive patients were managed by predefined surgical guidelines differentiating low-risk patients from patients at risk for dissemination requiring systematic lymphadenectomy. Low risk was defined as grade 1 or 2 endometrioid type with myometrial invasion (MI) ≤ 50% and primary tumor diameter (PTD) ≤ 2 cm. Pelvic and para-aortic lymph nodes were submitted separately, with nodes identified from all 8 pelvic and 4 para-aortic node-bearing basins. Surgical quality assessments examined median node counts (primary surrogate for quality) and nodes harvested above and below the IMA and excised gonadal veins (secondary surrogates). Results Lymphadenectomy was not required in 27% of patients (all low risk) and in 33% ( n = 112) of endometrioid cases. However, 22 patients (20%) of this latter cohort had lymphadenectomy and all lymph nodes were negative. Sixty-three (22%) of 281 patients undergoing lymphadenectomy had lymph node metastases: both pelvic and para-aortic in 51%, only pelvic in 33%, and isolated to the para-aortic area in 16%. Therefore, 67% of patients with lymphatic dissemination had para-aortic lymph node metastases. Furthermore, 77% of patients with para-aortic node involvement had metastases above the IMA, whereas nodes in the ipsilateral para-aortic area below the IMA and ipsilateral common iliac basin were declared negative in 60% and 71%, respectively. Gonadal veins were excised in 25 patients with para-aortic node metastases; 7 patients (28%) had documented metastatic involvement of gonadal veins or surrounding soft tissue. Conclusions The high rate of lymphatic metastasis above the IMA indicates the need for systematic pelvic and para-aortic lymphadenectomy (vs sampling) up to the renal vessels. The latter should include consideration of excision of the gonadal veins. Conversely, lymphadenectomy does not benefit patients with grade 1 and 2 endometrioid lesions with MI ≤ 50% and PTD ≤ 2 cm.

PCR-DGGE analysis of lactic acid bacteria and yeast dynamics during the production processes of three varieties of Panettone

To study lactic acid bacteria (LAB) and yeast dynamics during the production processes of sweet-leavened goods manufactured with type I sourdoughs. Fourteen sourdough and dough samples were taken from a baking company in central Italy during the production lines of three varieties of Panettone. The samples underwent pH measurements and plating analysis on three solid media. The microbial DNA was extracted from both the (sour)doughs and the viable LAB and yeast cells collected in bulk, and subjected to PCR-denaturing gradient gel electrophoresis (DGGE) analysis. The molecular fingerprinting of the cultivable plus noncultivable microbial populations provide evidence of the dominance of Lactobacillus sanfranciscensis, Lactobacillus brevis and Candida humilis in the three fermentation processes. The DGGE profiles of the cultivable communities reveal a bacterial shift in the final stages of two of the production processes, suggesting an effect of technological parameters on the selection of the dough microflora. Our findings confirm the importance of using a combined analytical approach to explore microbial communities that develop during the leavening process of sweet-leavened goods. In-depth studies of sourdough biodiversity and population dynamics occurring during sourdough fermentation are fundamental for the control of the leavening process and the manufacture of standardized, high-quality products.

Life cycle ofRickettsia slovacain L929 cell line studied by quantitative real-time PCR and transmission electron microscopy

Rickettsia slovaca, a member of spotted fever rickettsiae, is an agent of a mild human disease known as Tibola or Debonel. Using quantitative real-time PCR we identified the highest point of multiplication of wild and standard type (strain B) of R. slovaca on the second vs. the fourth day postinfection. Comparing both types of R. slovaca by transmission electron microscopy substantiated different cytopathological and morphological changes in infected cells and other differences, for example a slight shift of stages during the life cycle that presented in a variety of forms and localization of the studied Rickettsia within the infected cells. Our study provides a valuable insight into the pathogenicity and virulence of R. slovaca.

Lot-splitting for inspection in a synchronised two-stage manufacturing process with finite production rates and random out-of-control shifts in the first stage

We consider a non-repetitive manufacturing environment where the first stage will successively process different types of items that require different set up modes. Optimal sublot sizes are determined by studying the trade-off between the cost and time spent in restoration and rework. In addition, we discuss the resulting economical batch sizes, number of sublots, and processing rates. Finally, we provide recommendations on how to design the material handling flow system to implement our suggested inspection policies. Some of the managerial implications we found is that quality improves significantly when Stage 2 is more responsive (has faster processing times) than Stage 1 and when large batch sizes are divided into more sublots. Depending on the relative magnitude of poor quality and rework costs, we show that there is a threshold for the batch size under which sublot formation becomes inefficient. ]Received 17 July 2007; Revised 30 September 2007; Accepted 12 October 2007]

Early impact and performance characteristics of an established anal dysplasia screening program: program evaluation considerations.

Background: Screening for invasive anal cancer and its precursors is being increasingly advocated as a response to increasing incidence among HIV-infected persons. We implemented a comprehensive screening program in 2001 and report our early experience to inform monitoring and evaluation of such programs. Our research aims were: (1) to estimate incidence of and mortality from invasive anal cancer (IAC) before (1995-2000) and after (2001-2005) screening program implementation and (2) to examine potential screening program quality indicators.Methods: The study cohort included all patients under care for HIV infection at UCSD Owen Clinic between 1995-2005. Person-time incidence rates (IR) and case survival of IAC were estimated for the pre-screening (1995-2000) and post-screening (2001-2005) periods. High resolution anoscopy (HRA) operator accuracy was estimated by kappa agreement between cyto-histologic comparisons. Program quality indicators included: (1) screening coverage; (2) percent technically unsatisfactory cytology smears; (3) time between 1st abnormal cytology and 1st HRA; and (4) time between last clinic visit and last cytology.Results:28 cases of IAC and 13,411 person-years were observed between 1995-2005. IRs (95% CI) pre-screening and post-screening were 199 and 216 per 100,000 person-years, respectively. There was no routine treatment of high grade squamous intraepithelial lesions (HSIL) during the study period. The percent of patients with IAC requiring chemoradiation decreased from 90.9% to 70.6% (p=0.36). There was a significant improvement in cyto-histologic agreement at HRA with increasing operator experience (r=0.92, p=0.025). Screening coverage was 73% of the target population. Among 14 providers, the percent unsatisfactory cytology smears averaged 27% but varied from 0 – 62%. The median time from 1st abnormal cytology to 1st HRA was 258 days. The median interval between the last cytology and the last clinic visit was 207 days.Conclusion:(1) The overall IR of IAC did not decline in the screening era and was higher than previous estimates for HIV cohorts; (2) stage shift to IAC of more favorable prognosis is a reasonable screening goal; (3) HRA accuracy varied by provider experience; (4) because of delay in access to HRA, digital rectal exam should be combined with cytology screening to detect palpable disease.

Quantifying the role of PSA screening in the US prostate cancer mortality decline.

To quantify the plausible contribution of prostate-specific antigen (PSA) screening to the nearly 30% decline in the US prostate cancer mortality rate observed during the 1990s. Two mathematical modeling teams of the US National Cancer Institute's Cancer Intervention and Surveillance Modeling Network independently projected disease mortality in the absence and presence of PSA screening. Both teams relied on Surveillance, Epidemiology, and End Results (SEER) registry data for disease incidence, used common estimates of PSA screening rates, and assumed that screening, by shifting disease from distant to local-regional clinical stage, confers a corresponding improvement in disease-specific survival. The teams projected similar mortality increases in the absence of screening and decreases in the presence of screening after 1985. By 2000, the models projected that 45% (Fred Hutchinson Cancer Research Center) to 70% (University of Michigan) of the observed decline in prostate cancer mortality could be plausibly attributed to the stage shift induced by screening. PSA screening may account for much, but not all, of the observed drop in prostate cancer mortality. Other factors, such as changing treatment practices, may also have played a role in improving prostate cancer outcomes.

Effects of a Mandibular Repositioning Appliance on Sleep Structure, Morning Behavior and Clinical Symptomatology in Patients with Snoring and Sleep-Disordered Breathing

Background: Mandibular repositioning appliances (MRAs) have become an established treatment for snoring and sleep-disordered breathing – though most studies only focused on the evaluation of respiratory variables. Methods: This single-blind, placebo-controlled case-series study investigated the effects of an individually adjustable MRA on psychopathology, macro-/microstructure of sleep, periodic leg movements, morning performance, mood/affect and psychophysiology. Fifty patients (37 males) aged 59.7 ± 10.3 years, suffering from primary snoring (7), mild (22), moderate (15) and severe apnea (6), spent 4 nights in the sleep laboratory (adaptation, placebo, drug and MRA night). The drug night is not subject of the present paper. Results: Confirmatory statistics showed an improvement of the snoring index by 72%. Descriptively, the apnea index and the apnea-hypopnea index normalized. A clinical improvement was seen in the Pittsburgh Sleep Quality Index, the Zung Anxiety/Depression Scales and the Epworth Sleepiness Scale. The restless legs syndrome also improved. Polysomnographically, sleep stages REM and 4 as well as REM latency increased, stage 3, movement time, stage shifts and periodic leg movements decreased, as did all arousal measures. Subjectively, morning well-being, drive, affectivity and wakefulness improved. Objectively, attention, motor and reaction time performance, critical flicker frequency as well as muscular strength increased, diastolic blood pressure and the pulse rate decreased. Conclusion: Apart from its good therapeutic effects on snoring and respiratory variables (snoring showed complete or partial response in 68%, the apnea-hypopnea index in 67% of the apnea patients), the MRA also improved psychopathology, objective and subjective sleep and awakening quality.

Cost effectiveness of mammography screening for Chinese women

Although the cost effectiveness of screening mammography in most western developed populations has been accepted, it may not apply to Chinese women, who have a much lower breast cancer incidence. The authors estimated the cost effectiveness of biennial mammography in Hong Kong Chinese women to inform evidence-based screening policies. For the current study, a state-transition Markov model was developed to simulate mammography screening, breast cancer diagnosis, and treatment in a hypothetical cohort of Chinese women. The benefit of mammography was modeled by assuming a stage shift, in which cancers in screened women were more likely to be diagnosed at an earlier disease stage. The authors compared costs, quality-adjusted life years (QALYs) saved, and life years saved (LYS) for 5 screening strategies. Biennial screening resulted in a gain in life expectancy ranging from 4.3 days to 9.4 days compared with no screening at an incremental cost of from US $1,166 to US $2,425 per woman. The least costly, nondominated screening option was screening from ages 40 years to 69 years, with an incremental cost-effectiveness ratio (ICER) of US $61,600 per QALY saved or US $64,400 per LYS compared with no screening. In probabilistic sensitivity analyses, the probability of the ICER being below a threshold of US $50,000 per QALY (LYS) was 15.3% (14.6%). The current results suggested that mammography for Hong Kong Chinese women currently may not be cost effective based on the arbitrary threshold of US $50,000 per QALY. However, clinicians must remain vigilant and periodically should revisit the question of population screening: Disease rates in China have been increasing because of westernization and socioeconomic development.