Cancer Incidence in Kentucky, Pennsylvania, and West Virginia: Disparities in Appalachia

CONTEXT: Composed of all or a portion of 13 states, Appalachia is a heterogeneous, economically disadvantaged region of the eastern United States. While mortality from cancer in Appalachia has previously been reported to be elevated, rates of cancer incidence in Appalachia remain unreported. PURPOSE: To estimate Appalachian cancer incidence by stage and site and to determine if incidence was greater than that in the United States. METHODS: Using 1994--1998 data from the central registries of Kentucky, Pennsylvania, and West Virginia, age-adjusted incidence rates were calculated for the rural and nonrural regions of Appalachia. These state rates were compared to rates from the Surveillance, Epidemiology, and End Results (SEER) program for the same years by calculating the adjusted rate ratio (RR) and a 95% confidence interval (CI). FINDINGS: Both the entire and rural Appalachian regions had an adjusted incidence rate for all cancer sites similar to the SEER rate (RR = 1.00 [95% CI, 1.00-1.01] and RR = 0.99 [95% CI, 0.99-1.00], respectively). However, incidence of cancer of the lung/ bronchus, colon, rectum, and cervix in Appalachia was significantly elevated (RR = 1.22 [95% CI, 1.20-1.23], 1.13 [95% CI, 1.11-1.14], 1.19 [95% CI, 1.16-1.22], and 1.12 [95% CI, 1.07-1.17], respectively). Incidence of cancer of the lung/bronchus and cervix in rural Appalachia was even more elevated (RR = 1.34 [95% CI, 1.31-1.36] and 1.29 [95% CI, 1.21-1.38], respectively). Incidence of unstaged disease for all cancer sites in Appalachia (RR = 1.06 [95% CI, 1.05-1.08]), particularly rural Appalachia (RR = 1.28 [95%CI, 1.25-1.301), was elevated. CONCLUSIONS: Cancer incidence in Appalachia was not found to be elevated. However, incidence of cancer of the lung/bronchus, colon, rectum, and cervix was elevated in Appalachia. The rates of unstaged cancer of every examined site were elevated in rural Appalachia, suggesting a lack of access to cancer health care.     

Conceptualizing youth empowerment within tobacco control.

This article presents a conceptual framework that was developed to guide a national evaluation of the American Legacy Foundation's (Legacy) Statewide Youth Movement Against Tobacco Use (SYMATU) program. This program was designed to develop youth-led, youth-directed initiatives within local communities. Two evaluation studies were designed and implemented from 2000 through 2003: a cross-site study that collected standard data elements across all 17 programs and a case study of five programs that collected formative data on variables thought to affect program implementation. In developing the youth empowerment (YE) conceptual framework, the authors started by reviewing literature to identify the concepts necessary for these types of initiatives and present a summary of their findings here. This article focuses on the development of the authors'overarching conceptual framework used to guide their evaluation studies. Other articles contained within this special issue present results from each of the SYMATU evaluation studies.     

Cholecystectomy: costs and health-related quality of life: a comparison of two techniques.

BACKGROUND: Outcomes of previous health economic evaluations comparing minilaparotomy cholecystectomy and laparoscopic cholecystectomy have been inconsistent. OBJECTIVE: To compare costs for minilaparotomy cholecystectomy and laparoscopic cholecystectomy and to study changes in quality of life induced by these operations. DESIGN: Single-blind, randomized controlled trial, run from 1 March 1997 to 30 April 1999. SETTING: One university hospital and four non-university hospitals in Sweden. MAIN MEASURE: : Cost and perceived health estimation according to the global quality of life instrument EuroQol-5D. RESULTS: Of 1719 cholecystectomy patients at five centres, 724 entered the trial and were treated with minilaparotomy cholecystectomy or laparoscopic cholecystectomy, 362 in each group. Total health care costs were less for minilaparotomy cholecystectomy than for laparoscopic cholecystectomy (median values US$2428 for minilaparotomy cholecystectomy versus US$2613 or US$3006 for laparoscopic cholecystectomy with 100 operations per year and reusable trocars or 50 operations per year and disposable trocars, respectively). There was no significant difference in total costs (including costs due to loss of production) between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with 100 operations per year and reusable trocars in laparoscopic cholecystectomy (US$3731 versus US$3649, respectively). However, in calculations assuming 50 operations per year and disposable trocars in laparoscopic cholecystectomy, this technique was more expensive than minilaparotomy cholecystectomy (US$4042 versus US$3731). Health-related quality of life was slightly but significantly lower for the minilaparotomy cholecystectomy group 1 week after surgery. One month and 1 year postoperatively no difference between the randomized groups was found. CONCLUSION: Total costs did not differ between minilaparotomy cholecystectomy and laparoscopic cholecystectomy with high-volume surgery and disposable trocars, whereas laparoscopic cholecystectomy was more expensive with fewer operations and disposable trocars. The gain in health-related quality of life with laparoscopic cholecystectomy compared with minilaparotomy cholecystectomy was small and of limited duration.     

The use of the source-skin distance measuring bridge indeed reduces skin teleangiectasia after interstitial boost in breast conserving therapy.

BACKGROUND AND PURPOSE: In 1990 the skin source measuring bridge was proposed as a tool to measure (1) the distance between the interstitial implant and the overlying skin during brachytherapy boost treatment as well as (2) the distances between the lateral source end and the exit point of the guide needle. The present study reports on the clinical experience using the source skin measuring bridge with respect to incidence and grade of teleangiectasia, and their relation to source skin distances and doses. PATIENTS AND METHODS: Two hundred and twenty-two breast cancer patients (229 breasts) treated between 1983 and 1996 with breast conserving therapy including a brachytherapy boost were scored on the occurrence of teleangiectasia. The minimum distance between the sources (above implant and laterally) and the skin surface were measured. RESULTS: If no bridge was used the appearance of teleangiectasia in the epiderm above the implant is 77, 63 and 50% for boost doses of 25, 20 and 15 Gy, respectively. For brachytherapy boost doses of 25 and 20 Gy and distances smaller than 10mm between the implant and the overlying epiderm, as determined with the skin source measuring bridge, the appearance of teleangiectasia was 78 and 46%, respectively. When respecting provisional dosimetry to spare the skin for a boost dose of 15 Gy, resulting in distances between 10 and 15 mm for the implant overlying skin and distances between 5 and 10 mm for the lateral skin, teleangiectasia can be reduced to a minimum (6.3% above and 3.3% laterally). While in a univariate analysis several parameters (use of the bridge, boost dose, boost modality, external beam therapy modality) were predictive factors, the use of the bridge remained the only significant variable in a multivariate analysis. CONCLUSIONS: The skin source measuring bridge reduces teleangiectasia after interstitial brachytherapy boost treatment. A hypothesis made previously relating teleangiectasia and source skin distances was verified and extended. Even when 3D planning is used, the bridge allows for a provisional calculation of the security margins between source positions and the skin at the time of BT implantation to assure a correct needle positioning from the beginning, instead of correcting dwell times later on to avoid unnecessary high skin doses.     

DNA methylation in anal intraepithelial lesions and anal squamous cell carcinoma.

PURPOSE: Anal intraepithelial neoplasia is associated with human papillomavirus infection and may progress to invasive squamous cell carcinoma (SCC), which is increasing in immunocompromised patients. We hypothesize that anal intraepithelial neoplasia is associated with abnormal DNA methylation and that detection of these events may be used to improve screening programs. EXPERIMENTAL DESIGN: Seventy-six patients were identified who underwent anal cytology screening and subsequent biopsy at our institution between 1999 and 2004. The specimens from these patients included 184 anal biopsies [normal, n = 57; low-grade squamous intraepithelial lesion (LSIL), n = 74; high-grade squamous intraepithelial lesion (HSIL), n = 41; and invasive SCC, n = 12] and 37 residual liquid-based anal cytology specimens (normal, n = 11; LSIL, n = 12; HSIL, n = 14). The methylation status of the following genes was determined for each biopsy and cytology sample using real-time methylation-specific PCR: HIC1, RASSF1, RARB, CDKN2A, p14, TP73, APC, MLH1, MGMT, DAPK1, and IGSF4. RESULTS: Methylation-specific PCR analysis of biopsy samples revealed that DNA methylation was more common in SCC and HSIL than LSIL and normal mucosa. Specifically, methylation of IGSF4 and DAPK1 was prevalent in SCC (75% and 75% of cases, respectively) and HSIL (59% and 71%, respectively) but was absent in LSIL and normal biopsy samples. Methylation profiles of cytologic samples were similar to those found in the biopsy samples. CONCLUSIONS: Aberrant DNA methylation is a frequent event in anal HSIL and SCC. Methylation of IGSF4 and DAPK1 is specific for HSIL and SCC, and may serve as a useful molecular biomarker.     

The impact of CYP2C9 genetics and oral contraceptives on cytochrome P450 2C9 phenotype.

CYP2C9-dependent drug metabolism is subject to large interindividual variation. To some extent, this is explained by genetic polymorphism with expression of enzyme variants that differ in catalytic activity. The aim of this study was to characterize the variation in CYP2C9 phenotype in relation to genotype, with further analysis of the CYP2C9 gene in metabolic outliers. A study population of 126 healthy white subjects were recruited and genotyped for the variant alleles, CYP2C9*1-3. In CYP2C9 phenotyping with losartan, three subpopulations were distinguished that differed in the number of CYP2C9*3 alleles (0, 1, or 2). A three-fold higher metabolic ratio (MR; urinary losartan/carboxymetabolite) was found comparing CYP2C9*1/*3 (n = 20) to CYP2C9*1/*1 (n = 81), but there was considerable variation within each genotype. Subjects genotyped as CYP2C9*1/*1, but with an unexpectedly slow oxidation of losartan, were selected for DNA-sequencing analysis of the CYP2C9 gene. Interestingly, single nucleotide polymorphisms (SNPs) could not be identified either in the 5'-flanking region, the nine exons, or exon-intron boundaries. However, sequencing of the CYP2C9 gene was also carried out in patients genotyped as CYP2C9*1/*1 but with an exceptionally low steady-state clearance of S-warfarin. Here, five different SNPs were identified. In further analysis of the healthy volunteers, it became evident that women on oral contraceptives (OCs) had slower oxidation of losartan (MR of losartan: 1.7) than women without OCs (MR of losartan: 0.86). This novel finding was not explained by a different frequency of variant alleles. In summary, CYP2C9 genotype and oral contraceptives both contribute to a large interindividual variation in CYP2C9 activity.     

Hamartochondroma Pleural Lesion Mimicking Liposarcoma: A Case Report

Heterogeneous masses developing in the pleural cavity are most often malignant and can pose diagnostic challenges. Fibrous tumors of the pleura, liposarcoma, thymoma or lipoma most frequently affect this anatomic area. Surgical exploration and resection are often mandatory to make the definitive diagnosis. We report the case of a 54-year-old women who presented with an epigastric and right sub costal pain. A complete preoperative workup revealed a large tissular and fatty mass in the right costo-diaphragmatic angle suggestive of liposarcoma. Surgical resection resulted in the surprising diagnosis of hamartochondroma.     

Twelve tips for crossborder curriculum partnerships in medical education

Abstract

Crossborder curriculum partnerships are a relatively new and fast-growing form of internationalization in which the curriculum that has been developed by one institution (the home institution) crosses borders and is implemented in another institution (the host institution). These partnerships aim to provide comparable learning experiences to the students in both institutions and are driven by a variety of motives, such as strengthening international networks, increasing financial gains, and stimulating research spinoffs. Although popular, crossborder curriculum partnerships are also criticized for their potentially low educational quality, failing to address fundamental differences in teaching and learning between the home and host institutions, and not addressing the educational needs of the host country’s health care system. Our aim is to provide guidance to those considering or engaged in designing, developing, managing, and reviewing a crossborder curriculum partnership or other forms of international educational partnerships in medical education. Drawing from research, personal, and institutional experiences in this area, we listed twelve tips categorized into four themes, which contribute to the establishment of sustainable partnerships that can withstand the aforementioned criticism.     

Functional implications of short‐term retinal detachment in porcine eyes: study by multifocal electroretinography

Purpose: The aim of the study was to determine the type and magnitude of detectable changes in pig multifocal electroretinography (mfERG) induced by the vitreoretinal surgical procedures necessary to gain access to the subretinal space. Methods: Twenty pigs underwent posterior segment surgery. Six animals had a vitrectomy (V), six had in addition a retinal bleb detachment (V + B); five had in addition a retinal diathermia on the bleb (V + B + D) and three received a retinotomy in the diathermized retinal area (V + B + D + R). mfERG evaluation was performed at baseline and 1 and 6 weeks postoperatively. Selected eyes were enucleated for histological evaluation. Results: The retinal detachments blebs all reattached spontaneously. All four surgical sequences resulted in slight, non‐significant changes in the mfERG peaks. A trend towards an amplitude reduction of the mfERG peaks N1, P1 and N2 were observed within the first postoperative week. After 6 weeks, all amplitudes had normalized. Of the implicit times only that of peak N1 (after retinal diathermia) was prolonged significantly at 1 week (P = 0.037). However, it returned to the preoperative level after 6 weeks. Histologically, the retinal detachment bleb was characterized by transient double layering of the retinal pigment epithelium (RPE) and loss photoreceptor outer segments. Conclusion: Access to the subretinal space in pigs can be gained without permanent detectable changes in the mfERG. A short‐term retinal detachment was found to cause only reversible electrophysiological and histological changes in the outer retina, which suggests that this procedure is tolerated well in the porcine retina. The size of the known destructive lesion (retinotomy) was too small to be detected, given the spatial resolution of the mfERG method applied. In the future, the presented protocol can be used to assess the functional outcome of surgery and transplantation in the subretinal space in pigs.     

Cocaine self-administration on a hold-down schedule of reinforcement in rats

Rationale and objective  Although many contingencies operating in the natural environment include continuous dimensions of responses and reinforcers, previous studies of drug self-administration have almost exclusively used discrete dimensions of responses (e.g., a lever press) and reinforcers (e.g., 1.0 mg/kg/injection cocaine). Therefore, the present study provides an initial examination under experimental conditions with both responses and reinforcers measured along continuous dimensions. Materials and methods  Cocaine-maintained responding was studied in rats under a novel, hold-down schedule of reinforcement wherein the duration of the response was directly related to the magnitude of the reinforcer. These conditions were established by activating the syringe pump when the lever was pressed down and turning the pump off when the lever was released. The concentration of cocaine available in the syringe was varied across sessions. Results  Cocaine self-administration was readily maintained under these conditions and remained stable across sessions. Responding was concentration dependent, with the number of responses and total duration of the response inversely related to concentration, and overall session intake of cocaine was stable across concentrations. In general, the duration of the responses were less than 0.5 s and did not vary as a function of concentration. Conclusions  Stability of responding under these schedule conditions was acquired quickly. This schedule of reinforcement may be useful for comparing across drug classes, can be extended for use with other types of responses and reinforcers, and may be more representative of the natural world where response-reinforcer contingencies are more likely to be experienced along continuous, rather than discrete, dimensions. Drake Morgan and Yu Liu contributed equally to this publication.