Allocation of health care resources in the neonatal and perinatal area �CCPS Symposium 1996

There have been publically expressed concerns about the costs and allocation of neonatal and perinatal health care resources in Canada and elsewhere for the past 15 years. This paper reports information from a symposium held during the 1996 Canadian Paediatric Society (CPS) annual meeting sponsored by the CPS Section on Perinatal Medicine. Experts in perinatal epidemiology, health care economics, public policy and finance, and consumer perspectives on the outcomes of neonatal and perinatal intensive care explored the following questions: How should the need for health care resources in the neonatal and perinatal area be objectively determined? When there are competing needs between the maternal-newborn area and other areas, how should these be rationalized? What evidence should be used (or should be available) to support the present use of resources? What evidence should be available (or is needed) to change or introduce new uses of resources? The conclusions indicated that there are no generally accepted methods to determine the allocation of health care resources but that considerations need to include population characteristics, desired outcomes, achievable results, values, ethics, legalities, cost-benefit analyses and political objectives. Information from families and adolescents who required the use of high technology and/or high cost programs will contribute individual, family and societal values that complement cost-efficacy analyses.     

Uncoupling cancer mutations reveals critical timing of p53 loss in sarcomagenesis

It is well accepted that cancer develops following the sequential accumulation of multiple alterations, but how the temporal order of events affects tumor initiation and/or progression remains largely unknown. Here, we describe a mouse model that allows for temporally distinct cancer mutations. By integrating a Flp-inducible allele of K-ras(G12D) with established methods for Cre-mediated p53 deletion, we were able to separately control the mutation of these commonly associated cancer genes in vitro and in vivo. We show that delaying p53 deletion relative to K-ras(G12D) activation reduced tumor burden in a mouse model of soft-tissue sarcoma, suggesting that p53 strongly inhibits very early steps of transformation in the muscle. Furthermore, using in vivo RNA interference, we implicate the p53 target gene p21 as a critical mediator in this process, highlighting cell-cycle arrest as an extremely potent tumor suppressor mechanism.     

A randomised controlled trial of treatment for idiopathic intracranial hypertension

The cause of idiopathic intracranial hypertension (IIH) remains unknown, and no consensus exists on how patients should be monitored and treated. Acetazolamide is a common treatment but has never been examined in a randomised controlled trial. The objectives of this pilot trial are to prospectively evaluate the use of acetazolamide, to explore various outcome measures and to inform the design of a definitive trial in IIH. Fifty patients were recruited from six centres over 23 months and randomised to receive acetazolamide (n = 25) or no acetazolamide (n = 25). Symptoms, body weight, visual function and health-related quality-of-life measures were recorded over a 12-month period. Recruited patients had typical features of mild IIH and most showed improvement, with 44% judged to have IIH in remission at the end of the trial. Difficulties with recruitment were highlighted as well as poor compliance with acetazolamide therapy (12 patients). A composite measure of IIH status was tested, and the strongest concordance with final disease status was seen with perimetry (Somers' D = 0.66) and optic disc appearance (D = 0.59). Based on the study data, a sample size of 320 would be required to demonstrate a 20% treatment effect in a substantive trial. Clinical trials in IIH require pragmatic design to involve sufficiently large numbers of patients. Future studies should incorporate weighted composite scores to reflect the relative importance of common outcome measures in IIH.     

Impact of Breast Density on the Presenting Features of Malignancy

Purpose

To determine the relationship between breast density, presenting features and molecular subtype of cancer, and surgical treatment received.

Methods

Retrospective review of a prospectively maintained database. Eligible patients had stage 1–3 cancer, were treated between 1/2005 and 6/2007, and had estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) measurements and films available for review. Density was classified at presentation as 1–4 using the Breast Imaging Reporting and Data System (BI-RADS) classification.

Results

1,323 patients were included. Significant differences across the four density groups were present in age, race, multicentricity/focality, and presence of an extensive intraductal component (EIC). When density was combined into two groups, after adjustment for age, only an EIC and mammographically occult cancer were significantly more common in the dense groups. Extremely dense breasts (BI-RADS density 4) more commonly had luminal A tumors (p = 0.05), lobular cancers (p = 0.03), multicentricity (p = 0.02), and occult tumors (p < 0.0001). Greater density was associated with increased mastectomy use, with 61% of the extremely dense group having mastectomy versus 43% of those of lesser density (p = 0.01).

Conclusions

Cancers in extremely dense breasts occur in younger women, are more often mammographically occult, and appear to be phenotypically different from those arising in other density groups. The more common use of mastectomy may be related to these features, although density itself is not a selection criterion for mastectomy.

     

A nomogram to predict postresection 5-year overall survival for patients with uterine leiomyosarcoma

BACKGROUND:

The clinical course of patients with uterine leiomyosarcoma (LMS) is difficult to predict with the currently available categorical staging systems of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). The objective of the current study was to develop and validate a novel, clinically relevant, individualized prognostic model for patients with uterine LMS.

METHODS:

Patients with uterine LMS who presented at the authors' institution from 1982 to 2008 were analyzed. The nomogram model was chosen based on the clinical evidence and statistical significance of the predictors, including age at diagnosis, tumor size, histologic grade, uterine cervix involvement, extrauterine spread, distant metastases, and mitotic index. Five‐year overall survival (OS) was the predicted endpoint. The concordance probability (CP) was used as a predictive accuracy measure and compared with the CP of current staging systems. The model was internally validated using 200 bootstrap samples to correct for over fitting.

RESULTS:

One hundred eighty‐five of 270 patients were eligible for the nomogram analysis. The median follow‐up was 5.4 years, and the median OS was 3.75 years (95% confidence interval, 3‐6 years). The CP of the newly developed nomogram was 0.67 (95% confidence interval, 0.63‐0.72). This was superior to predictions based on AJCC and FIGO staging. The bootstrap‐validated CP was 0.65 with good calibration accuracy.

CONCLUSIONS:

The authors developed and internally validated a uterine LMS‐specific nomogram to predict 5‐year OS. This novel, individualized prognostic model outperforms traditionally used categorical staging systems and may be useful for patient counseling and for better selection of patients for adjuvant therapy trials. Cancer 2012;. © 2011 American Cancer Society.     

Digit ratio (2D:4D) is associated with gastric cancer

Background

Sex steroid exposure during early human development may influence disease susceptibility. Digit ratio (2D:4D) is a putative marker for prenatal hormone exposure and sensitivity, as well as the action of genes closely related to carcinogenesis. Digit ratio could act as a possible marker for cancer predisposition.

Aims

The aim of this study is to investigate the possible correlations between right hand, left hand and right minus left (R − L) 2D:4D and gastric cancer (GCA) in men and women and assess the correlations with tumor staging and histological diagnosis.

Methods

Digital images of the right and left hand palms of patients diagnosed with GCA (n = 57, 42 males, 15 females) and age and sex-matched controls (n = 59, 41 males, 18 females) were obtained. Means for 2D:4D were compared. Data were analyzed by repeated-measures one-way ANOVA and Student's t-test for finger measurements and group comparisons and Pearson's and Spearman's tests for correlations with tumor staging (α = 0.05).

Results

GCA group presented significantly higher left 2D:4D, but significantly lower R − L in comparison to healthy controls, particularly so for males. Digit ratio did not correlate to clinical staging or TNM staging. However, low R − L was significantly related to adenocarcinomas.

Conclusions

Early developmental conditions, including prenatal testosterone seem to play a role on the malignant transformation of gastric lesions. The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer. The findings suggest that 2D:4D could add to the list of etiological factors and be a putative marker for the screening of patients’ susceptibility to develop gastric cancer.     

Conservative treatment protocol of odontogenic keratocyst: a preliminary study.

PURPOSE: The objective of this study was to report our experience with the treatment of 30 odontogenic keratocyst (OKC) patients with a conservative treatment protocol based on decompression with reference to the recurrence rate. PATIENTS AND METHODS: Twenty-eight patients (19 females, 9 males) with 30 OKCs attended the OMS Department of the Piracicaba Dental School of Campinas State University between 1995 and 2003. Age range was 13 to 69 years (mean, 30 years of age). Initial biopsy was carried out in all patients and the OKCs were diagnosed after histological examination by the Oral Pathology Department. The cases were treated according to the treatment employed in this department, consisting mainly of decompression and curettage of the remaining lesion. The average follow-up for the 28 cases was 24.89 months (+/-9.74). RESULTS: The majority of the lesions (16 patients, 53.3%) occurred in the angle of the mandible and mandibular ramus. The most common histological pattern of OKC was parakeratinized (66.6%) and 13 of 28 patients presented impacted teeth associated with the lesion. The mean time for decompression was 9.27 months. Recurrence occurred in 4 patients (14.3%) with 4 OKCs. These patients were treated initially with decompression and curettage (2 cases), or with decompression only (2 cases). All the cases were monitored continuously with panoramic radiographies and clinical evaluations. CONCLUSIONS: The treatment protocol for OKC based on decompression offers a conservative and effective option with low morbidity and similar recurrence rates to those reported in the literature. The systematic and long-term post-surgical follow-up is considered to be a key element for successful results.