Tailoring capture-recapture methods to estimate registry-based case counts based on error-prone diagnostic signals.

Surveillance research is of great importance for effective and efficient epidemiological monitoring of case counts and disease prevalence. Taking specific motivation from ongoing efforts to identify recurrent cases based on the Georgia Cancer Registry, we extend recently proposed "anchor stream" sampling design and estimation methodology. Our approach offers a more efficient and defensible alternative to traditional capture-recapture (CRC) methods by leveraging a relatively small random sample of participants whose recurrence status is obtained through a principled application of medical records abstraction. This sample is combined with one or more existing signaling data streams, which may yield data based on arbitrarily non-representative subsets of the full registry population. The key extension developed here accounts for the common problem of false positive or negative diagnostic signals from the existing data stream(s). In particular, we show that the design only requires documentation of positive signals in these non-anchor surveillance streams, and permits valid estimation of the true case count based on an estimable positive predictive value (PPV) parameter. We borrow ideas from the multiple imputation paradigm to provide accompanying standard errors, and develop an adapted Bayesian credible interval approach that yields favorable frequentist coverage properties. We demonstrate the benefits of the proposed methods through simulation studies, and provide a data example targeting estimation of the breast cancer recurrence case count among Metro Atlanta area patients from the Georgia Cancer Registry-based Cancer Recurrence Information and Surveillance Program (CRISP) database.

Vestibular Schwannoma Cerebellopontine Angle Position Impacts Facial Outcome.

OBJECTIVES/HYPOTHESIS: To determine the impact of vestibular schwannoma (VS) position relative to the internal auditory canal (IAC) on postoperative facial nerve function and extent of surgical resection. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review of patients undergoing resection of large (≥25 mm) VSs. Outcome measures included early (≤1 month) facial function, long-term (≥1 year) facial function and extent of resection. Tumor measurements included the greatest dimension, dimension anterior to the IAC axis, dimension posterior to the IAC axis, and a ratio of posterior-to-anterior dimension (PA ratio). RESULTS: A total of 127 patients met inclusion criteria. In early follow-up, 60% patients had good (House-Brackmann I-II), and 40% patients had poor (House-Brackmann III-VI) facial function. In long-term follow-up, 71% patients had good, and 29% patients had poor facial function. A total of 72% of patients underwent gross total resection (GTR) of their tumors. Patients with good facial function had significantly larger PA ratios than patients with poor function both early and long term; however, greatest dimension was the more clearly significant independent predictor of facial outcomes. A larger PA ratio was observed in patients in whom GTR was achieved, but this association was potentially confounded by surgeon preferences and was not statistically significant after controlling for surgical site. CONCLUSIONS: This study demonstrates that VS position relative to the IAC axis can be used along with tumor size to predict postoperative facial outcomes. A greater proportion of tumor posterior to the IAC axis was associated with significantly better facial outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1093-1098, 2022.

Differences in inpatient and outpatient hepatitis C virus prevalence and linkage to care rates in a safety net hospital hepatitis C screening program.

BACKGROUND AND AIM: Routine screening for hepatitis C virus (HCV) infection is crucial in identifying the 50% of infected persons unaware of their infection. We added an inpatient screening initiative to our successful outpatient HCV screening program in an urban, safety-net hospital. METHODS: From March 2017 to December 2019, HCV screening was performed in inpatient and outpatient settings at Grady Health System. We compared care cascade outcomes, including anti-HCV testing, RNA testing, and linkage to care (LTC) between these settings. RESULTS: A total of 29 751 patients were tested for anti-HCV: 8883 inpatients and 20 868 outpatients. The anti-HCV population was predominantly Black (76.2%) and male (67.9%). The total anti-HCV prevalence was 8.9%, with 14% of inpatients and 6.7% of outpatients testing positive. RNA testing was performed on 86%. The prevalence of active HCV infection was 59.3% in those that were anti-HCV positive; inpatient prevalence was 66%, and outpatient was 53.8%. Of those with active infection, 67.5% were linked to care (57.3% of inpatients and 77.8% of outpatients). CONCLUSION: We found significant differences in prevalence of anti-HCV and LTC rates between inpatients and outpatients during an HCV screening program. Higher anti-HCV prevalence among inpatients may be due a higher prevalence of non-birth year HCV risk factors. LTC rates were lower in the inpatient setting despite a robust linkage strategy. The striking prevalence of HCV in both settings warrants continued screening, expansion to additional settings, and novel strategies to improve inpatient linkage rates, especially in the setting of new universal HCV screening guidelines.

Serum polybrominated diphenyl ether concentrations and thyroid function in young children.

Thyroid hormones are essential for proper neurodevelopment in early life. There is evidence that exposure to polybrominated diphenyl ethers (PBDEs) affects thyroid function, but previous studies have been inconsistent, and no studies among children have been conducted in the United States where PBDE levels are particularly high. Serum levels of seven PBDE congeners and thyroid hormones and other thyroid parameters were measured in 80 children aged 1-5 years from the southeastern United States between 2011 and 2012. Parents of the children completed questionnaires with details on demographics and behaviors. Multivariate linear regression models were used to estimate the associations between serum PBDE levels, expressed as quartiles and as log-transformed continuous variables, and markers of thyroid function. BDE-47, 99, 100 and 153 were detected in >60% of samples, and were summed (∑PBDE). PBDE congeners and ∑PBDE were positively associated with thyroid-stimulating hormone (TSH). A log-unit increase in ∑PBDE was associated with a 22.1% increase in TSH (95% CI: 2.0%, 47.7%). Compared with children in the lowest quartile of ∑PBDE exposure, children in higher quartiles had greater TSH concentrations as modeled on the log-scale (second quartile: ß=0.32, 95% confidence interval (CI): -0.09, 0.74; third quartile: ß=0.44, 95% CI: 0.04, 0.85; and fourth quartile: ß=0.49, 95% CI: 0.09, 0.89). There was also a tendency toward lower total T4 and higher free T3 with increasing PBDE exposure. Results suggest that exposure to PBDEs during childhood subclinically disrupts thyroid hormone function, with impacts in the direction of hypothyroidism.

Outcomes of robotic sacrocolpopexy: a systematic review and meta-analysis.

OBJECTIVES: Robotic sacrocolpopexy has been rapidly incorporated into surgical practice without comprehensive and systematically published outcome data. The aim of this study was to systematically review the currently published peer-reviewed literature on robotic-assisted laparoscopic sacrocolpopexy with more than 6 months of anatomic outcome data. METHODS: Studies were selected after applying predetermined inclusion and exclusion criteria to a MEDLINE search. Two independent reviewers blinded to each other's results abstracted demographic data, perioperative information, and postoperative outcomes. The primary outcome assessed was anatomic success rate defined as less than or equal to pelvic organ prolapse quantification system (POP-Q) stage 1. A random effects model was performed for the meta-analysis of selected outcomes. RESULTS: Thirteen studies were selected for the systematic review. Meta-analysis yielded a combined estimated success rate of 98.6% (95% confidence interval, 97.0%-100%). The combined estimated rate of mesh exposure/erosion was 4.1% (95% confidence interval, 1.4%-6.9%), and the rate of reoperation for mesh revision was 1.7%. The rates of reoperation for recurrent apical and nonapical prolapse were 0.8% and 2.5%, respectively. The most common surgical complication (excluding mesh erosion) was cystotomy (2.8%), followed by wound infection (2.4%). CONCLUSIONS: The outcomes of this analysis indicate that robotic sacrocolpopexy is an effective surgical treatment of apical prolapse with high anatomic cure rate and low rate of complications.

Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial.

UNLABELLED: BACKGROUND: Vitamin D insufficiency is common in cystic fibrosis (CF) and vitamin D repletion may have an important role in improving clinical outcomes in CF. This randomized, placebo-controlled, pilot study examined the feasibility and impact of a single, large dose of cholecalciferol on vitamin D status and clinical outcomes in subjects with CF. METHODS: Thirty adults with were randomized in a double-blinded, pilot study to receive 250,000 IU cholecalciferol or placebo within 48 h of hospital admission for a pulmonary exacerbation. Concentrations of 25-hydroxyvitamin D (25(OH)D), clinical outcomes and potential adverse events were assessed up to one year after randomization. Mixed effects linear regression models were used to evaluate the difference in mean serum concentrations and log-rank analyses were used to evaluate survival. RESULTS: Data from all subjects was analyzed. Serum 25(OH)D concentrations increased from a mean of 30.6 ± 3.2 ng/mL to 58.1 ± 3.5 ng/mL (p < 0.001) at one week and 36.7 ± 2.6 ng/mL by 12 weeks (p = 0.06) in the vitamin D group; in contrast, serum 25(OH)D concentrations remained unchanged in the placebo group. Unadjusted, one-year survival and hospital-free days were increased in the vitamin D group (p = 0.029, p = 0.036; respectively). There was also a trend toward increased IV antibiotic therapy-free days in the vitamin D group (p = 0.073). There were no signs of hypervitaminosis D or adverse events. Serum PTH and calcium concentrations were similar across both groups. CONCLUSIONS: In this pilot study, a single, oral bolus of cholecalciferol increased serum 25(OH)D concentrations and was associated with a trend toward improved clinical outcomes in CF subjects hospitalized for a pulmonary exacerbation. Further investigation is needed into the clinical impact of improved vitamin D status in patients with CF.

Likelihood-based methods for regression analysis with binary exposure status assessed by pooling.

The need for resource-intensive laboratory assays to assess exposures in many epidemiologic studies provides ample motivation to consider study designs that incorporate pooled samples. In this paper, we consider the case in which specimens are combined for the purpose of determining the presence or absence of a pool-wise exposure, in lieu of assessing the actual binary exposure status for each member of the pool. We presume a primary logistic regression model for an observed binary outcome, together with a secondary regression model for exposure. We facilitate maximum likelihood analysis by complete enumeration of the possible implications of a positive pool, and we discuss the applicability of this approach under both cross-sectional and case-control sampling. We also provide a maximum likelihood approach for longitudinal or repeated measures studies where the binary outcome and exposure are assessed on multiple occasions and within-subject pooling is conducted for exposure assessment. Simulation studies illustrate the performance of the proposed approaches along with their computational feasibility using widely available software. We apply the methods to investigate gene-disease association in a population-based case-control study of colorectal cancer.

A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade.

Chromophobe renal cell carcinoma (RCC) is a histologic subtype of RCC that portends a favorable prognosis. It is controversial whether the Fuhrman nuclear grade of chromophobe RCC has prognostic utility. Irregular nuclei, prominent nucleoli, and nuclear pleomorphism are inherently present in chromophobe RCC. Hence, the Fuhrman nuclear grade is higher even though the majority of these tumors have a favorable outcome. In this study, the prognostic utility of a novel 3-tiered tumor grading system in which the innate nuclear atypia of chromophobe RCC was discounted, herein referred to as chromophobe tumor grade from a series of 124 chromophobe RCC, was compared with Fuhrman nuclear grade. Chromophobe tumor grade is based on the assessment of geographic nuclear crowding and anaplasia. The Fuhrman nuclear grade distribution between the tumors was grade 1 (1%), grade 2 (19%), grade 3 (74%), and grade 4 (6%), whereas the chromophobe tumor grade distribution was grade 1 (74%), grade 2 (16%), and grade 3 (10%). Neither Fuhrman nuclear grade nor chromophobe tumor grade was significantly associated with patient's age or sex and chromophobe RCC cell types, but both showed a significant association with tumor size. Both Fuhrman nuclear grade and chromophobe tumor grade showed statistically significant positive associations with broad alveolar growth, necrosis, vascular invasion, and with pathologic stage; however, all these associations tended to be dictated by tumors with sarcomatoid change. When tumors with sarcomatoid change were excluded, a strong positive association persisted between chromophobe tumor grade and pathologic stage. In contrast, there was no such association between Fuhrman nuclear grade and stage in nonsarcomatoid chromophobe RCCs. Characterizing aggressive chromophobe RCC with aggressive behavior with the time from surgery to first occurrence of metastasis, local recurrence, or death owing to disease, we found that both Fuhrman nuclear grade and chromophobe tumor grade were highly associated with adverse outcome. However, as with the pathologic stage, only a significant association between chromophobe tumor grade and outcome was retained among nonsarcomatoid chromophobe RCCs. Multivariable Cox regression analysis also tended to support chromophobe tumor grade rather than Fuhrman nuclear grade as an independent predictor of adverse outcome, controlling for other univariably significant risk factors [estimated relative hazard=3.68 (P=0.026) vs. 1.86 (P=0.42)]. In conclusion, the novel chromophobe tumor grading system proposed herewith provides superior prognostic value to that of the Fuhrman nuclear grade in chromophobe RCC and will potentially help stratify patients of chromophobe RCC who are at a greater risk of disease progression.

Sample size calculations for evaluating a diagnostic test when the gold standard is missing at random.

Performance of a diagnostic test is ideally evaluated by a comparison of the test results to a gold standard for all the patients in a study. In practice, however, it is common for a subset of study patients to have the gold standard not verified (missing) due to ethical or expense considerations. Sensitivity and specificity are often used as the relevant test performance measures and a joint confidence region (CR) for sensitivity and specificity can summarize the precision of estimates. In this paper, we present an approach to sample size computations when designing a study in which the gold standard is considered to be missing at random (MAR). We calculate the needed increase in sample size to ensure that the joint CR under MAR falls inside the boundaries of the joint CR derived for data with no missingness present.

Dynamic hydrodistention of the ureteral orifice: a novel grading system with high interobserver concordance and correlation with vesicoureteral reflux grade.

PURPOSE: We evaluated the usefulness and interobserver concordance of a novel grading system for dynamic ureteral hydrodistention. MATERIALS AND METHODS: Between May 1, 2002 and July 1, 2008 the hydrodistention grade in 697 ureters was prospectively assigned and recorded, including H0-no hydrodistention, H1-ureteral orifice open but tunnel not evident, H2-tunnel seen only and H3-extravesical ureter visualized. Specifically 489 refluxing ureters (vesicoureteral reflux group) were compared to 100 normal control ureters (normal control group). Additionally, the posttreatment hydrodistention grade in 56 ureters in which surgery for reflux failed was compared to that in 52 ureters with successful surgery. Hydrodistention grades assigned to an additional 77 ureters by 3 blinded observers were compared to assess the interobserver concordance of this system. RESULTS: Vesicoureteral reflux and hydrodistention grades correlated significantly (p <0.001). Ureters with a higher reflux grade also showed a higher hydrodistention grade. The normal control group (mean +/- SEM hydrodistention grade 0.62 +/- 0.07) showed a statistically lower hydrodistention grade than the reflux groups (overall mean hydrodistention grade 2.26 +/- 0.01). Mean posttreatment hydrodistention grade in the failed reflux surgery group was statistically higher than that in the mean successful reflux surgery group (2.03 +/- 0.09 vs 1.33 +/- 0.08). By defining the degree of hydrodistention as normal (H0-H1) and abnormal (H2-H3) the concordance between observers was 95% and 96%. CONCLUSIONS: The dynamic hydrodistention classification is a reliable method of evaluating the presence or absence of vesicoureteral reflux as it correlates significantly with radiographic reflux grade. It has high interobserver concordance.

Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases.

The aggregate literature suggests that chromophobe renal cell carcinoma (RCC) is biologically a tumor of low malignant potential with reported 5-year and 10-year survival rates of 78% to 100% and 80% to 90%, respectively. The conventional prognostic parameters that determine the outcome of the tumors that progress remain to be fully characterized. Clinicopathologic features of 145 cases were correlated with outcome. The mean age of the patients was 59 years (range, 27 to 82) and the male to female ratio was 1.1:1. Most tumors were well circumscribed and averaged 8.0 cm (range, 1.0 to 30.0 cm); multifocality and bilaterality were present in 8% and 3% of patients. Sixty (41%) were eosinophilic variant (greater than 80% eosinophilic cells), 18 (12%) were classic type (greater than 80% pale cells), and 67 (46%) were mixed (containing variable admixture of pale and eosinophilic cells). A subset of eosinophilic chromophobe RCC contained or had areas similar to renal oncocytomas. These tumors tended to be more commonly bilateral (11%) and multifocal (22%) and were not associated with necrosis or sarcomatoid change. Sarcomatoid change was present in 12/145 (8%) tumors. By histologic grade, 1%, 19%, 74%, 6% were Fuhrman nuclear grade 1, 2, 3, and 4. Nineteen percent, 21%, 28%, 13%, 4%, 1%, and 3% were pT (2002) stage pT1a, pT1b, pT2, pT3a, pT3b, pT3c, and pT4 tumors. Two percent tumors were pN1 at presentation and 2.8% tumors were M1 at presentation. Follow-up (1 to 182 mo, mean 48 mo, median 37 mo) was available in 123 cases. Disease progression (local recurrence 4, metastasis 15, and/or death 10) was seen in 20 patients. In univariable analysis, tumor size (P=0.025), pT stage (P<0.001), broad alveolar architecture (P=0.012), Fuhrman nuclear grade (P<0.001), microscopic tumor necrosis (P=0.001), vascular invasion (P=0.020), and sarcomatoid change (P< or =0.001) were associated with progression. A multivariable Cox regression model revealed sarcomatoid change (P=0.013, estimated relative hazard 4.7), microscopic necrosis (P=0.020, relative hazard=3.5), and pT stage (P=0.025, relative hazard 3.4) as independent predictors of aggressive chromophobe RCC. Although the large majority of chromophobe RCCs have a favorable prognosis, a distinct subset of patients progress. The pT stage of tumor, tumor necrosis, and sarcomatoid change all predict aggressive phenotype of chromophobe RCC. The adverse presence of these features in a nephrectomy specimen with chromophobe RCC warrants active surveillance, and these patients may be candidates for adjuvant therapies as they become available.

A decay model for assessing polybrominated biphenyl exposure among women in the Michigan Long-Term PBB Study.

The Michigan Long-Term PBB Study was established following exposure to polybrominated biphenyls (PBBs) in the early 1970s. Serum samples from cohort members were analyzed for PBB during 1976-1993. More than 20 years following this industrial incident, some participants still had measurable serum PBB concentration levels. Thus, there is continuing interest in understanding the elimination of PBB from the body. In the present study, we estimated serum PBB decay and investigated the effects of covariates on serum PBB decay rates among 406 female cohort members. We developed a decay model using a general linear mixed model, which attributes unique intercept and slope estimates for each individual while borrowing information across individuals for predicting these quantities. Age at exposure and body mass index (BMI) at the initial measurement were time-independent covariates. Time since exposure, smoking history, pregnancy status, and breast-feeding status were time-dependent covariates. Higher BMI was associated with a slower decay rate; smokers had a faster decay rate than nonsmokers; and increasing age at exposure was marginally associated with a slower decay rate. Our results suggest a faster serum PBB decay rate for women who breast-fed during the interval between serum PBB measurements. To evaluate the predictive performance of our modeling approach, we compared the results from this model with those from a previously developed ordinary least squares (OLS) two-stage decay model. The mixed-effects decay model predicted the observed serum PBB concentration levels significantly better than the OLS two-stage decay model (mixed-effects model, r=0.93; OLS two-stage model, r=0.86; P<0.0001).

Counting alleles in single lesions of prostate tumors from ethnically diverse patients.

BACKGROUND: The presence of racial disparities in incidence and mortality rates are well-documented for prostate cancer. Nevertheless, it is unclear whether such disparities are due to genetic alterations that are involved in prostate cancer initiation. Here, we evaluated chromosome 8p allelic loss in a racially diverse cohort. METHODS: Laser-capture microdissection was used to isolate tumors cells from individual lesions in 153 prostate cancer patients, and 8p allelic status was determined by "counting alleles." Statistical analyses examined the association between pathologic predictors and biochemical recurrence. RESULTS AND CONCLUSIONS: Thirty percent of prostate lesions were missing an 8p allele at tumor initiation, while 51% of lesions lost an 8p allele during tumor progression. Biochemical recurrence after radical prostatectomy could be reliably predicted by surgical margin status only in lesions with extensive 8p allelic loss. There was, however, no racial disparity in 8p allelic loss at tumor initiation or during tumor progression, suggesting that the molecular event involved was similar between Caucasians and Africa Americans (CA and AA). Nonetheless, racial differences were present in values of prognostic factors for recurrence. Gleason score was the most important predictor of recurrence (HR=3.1, 95% CI=1.1, 9.2) in AA, while among CA, pathologic stage (HR=3.3, 95% CI=1.5, 7.6) and surgical margin (HR=4.7, 95% CI=1.8, 12.6) were the most important. Therefore, racial disparity in prostate cancer may be due to other factors that are involved in prostate cancer development.

Comparison of recovery after mitral valve repair and replacement.

OBJECTIVE: We sought to examine the comparative improvement in health status after primary mitral valve repair versus replacement in patients with mitral valve regurgitation in a longitudinal setting. METHODS: We prospectively followed 267 patients with mitral valve regurgitation who underwent primary mitral valve repair (n = 163) and replacement (n = 104) between January 2002 and January 2005. Health status was evaluated at baseline and 1, 3, and 12 months after surgery with the validated short-form 36 and analyzed using generalized estimating equations with adjustment for propensity scores. RESULTS: Compared with patients undergoing mitral valve replacement, patients requiring valve repair were younger and more likely to be male. The probability of postsurgical readmission because of cardiac events was low and similar between the two treatment groups. New York Heart Association functional class was significantly improved after both procedures, with better improvement achieved by mitral valve repair (P < .01). For both treatment groups, scores for most of the short-form 36 domains were depressed at 1 month; however, after 3- and 12-month lags, dramatic improvements were achieved in most of the domains. Adjusted changes in the physical component score were similar between the two arms at each follow-up. For the mental component score, patients who underwent repair showed significant improvements compared with patients who underwent replacement at both 3 months (difference: 4.84 points, P = .005) and 12 months (difference: 5.92 points, P < .001). CONCLUSIONS: Our study suggests that after mitral valve surgery, there is significant improvement in New York Heart Association functional class and health status, especially in patients undergoing mitral valve repair.

Inference for case-control studies when exposure status is both informatively missing and misclassified.

In case-control studies, it is common for a categorical exposure variable to be misclassified. It is also common for exposure status to be informatively missing for some individuals, in that the probability of missingness may be related to exposure. Procedures for addressing the bias due to misclassification via validation data have been extensively studied, and related methods have been proposed for dealing with informative missingness based on supplemental sampling of some of those with missing data. In this paper, we introduce study designs and analytic procedures for dealing with both problems simultaneously in a 2x2 analysis. Results based on convergence in probability illustrate that the combined effects of missingness and misclassification, even when the latter is non-differential, can lead to naïve exposure odds ratio estimates that are inflated or on the wrong side of the null. The motivating example comes from a case-control study of the association between low birth weight and the diagnosis of breast cancer later in life, where self-reported birth weight for some women is supplemented by accurate information from birth certificates.

New contralateral vesicoureteral reflux following dextranomer/hyaluronic Acid implantation: incidence and identification of a high risk group.

PURPOSE: To our knowledge the incidence of NCVUR following the endoscopic treatment of VUR with Dx/HA has not been reported previously. We evaluated the outcomes in a group of patients to determine the incidence, and to attempt to identify risk factors. MATERIALS AND METHODS: A total of 126 children with primary unilateral VUR underwent unilateral Dx/HA implantation at our institutions. The incidence of NCVUR was determined by postoperative VCUG. Indications for surgery, patient age and gender, preoperative grade of VUR and volume of Dx/HA injected were assessed as possible risk factors for NCVUR. RESULTS: Of the patients 96 (76.2%) were female, and mean age was 4.8 years. The principal indications for Dx/HA implantation were persistent reflux in 56 patients (44.4%) and primary therapy in 51 (40.5%). At followup VCUG 17 patients (13.5%) had NCVUR. No variable independently appeared to influence the incidence of NCVUR. Statistical analysis suggests that females younger than 5 years have an increased incidence of NCVUR (13 of 62, or 21% vs 4 of 64, or 6.3% of the remaining patients, p = 0.016). CONCLUSIONS: NCVUR occurred in approximately 13% of our patients. Patients with higher preoperative VUR grade or a lower number of preoperative VCUGs and those undergoing treatment as primary therapy did not have an increased incidence. Girls younger than 5 years had the highest incidence of NCVUR, and initial bilateral injection may be a consideration for this group. Further effort directed at identifying the etiology and risk factors for NCVUR is needed.

North American white mitochondrial haplogroups in prostate and renal cancer.

PURPOSE: While the mitochondrion is known to be a key mediator of apoptosis, there has been little inquiry into the inheritance pattern of mitochondria in patients with cancer. We compared the mtDNA haplotype in patients with prostate and renal cancer to that in controls to determine if there is an association between mitochondrial genotype and cancer. MATERIALS AND METHODS: Haplotyping was performed using polymerase chain reaction/digest identification of key polymorphic sites in the mitochondrial genome. A total of 121 and 221 white men with renal and prostate cancer, respectively, were identified following pathological confirmation of cancer, while 246 white controls were selected randomly from a bank of cadaveric organ donor DNA. Statistical analysis was performed and ORs were calculated. RESULTS: Mitochondrial haplogroup U was a highly significant risk factor for prostate and renal cancer vs controls (16.74% and 20.66% vs 9.35%, Fisher's exact test p = 0.019 and 0.005, respectively). The association remained statistically significant in renal cancer even after Bonferroni adjustment for multiple comparisons. Haplogroup U carried an OR of 1.95 for prostate cancer and an OR of 2.52 for renal cancer. CONCLUSIONS: The inheritance of mitochondrial haplogroup U is associated with an approximately 2-fold increased risk of prostate cancer and 2.5-fold increased risk of renal cancer in white North American individuals. Therefore, individuals with this mitochondrial haplotype are in a high risk group. Because mitochondrial haplogroup U is found in 9.35% of the white United States population, there are more than 20 million individuals in this high risk group.

Assay validation for left-censored data.

In laboratory validation studies, it is often important to assess agreement between two assays, based on different techniques. Oftentimes, both assays have lower limits of detection and thus measurements are left censored. For example, in studies of Human Immunodeficiency Virus (HIV), the branched DNA (bDNA) assay was developed to quantify HIV-1 RNA concentrations in plasma. Validation of newer assays, such as the RT-PCR (reverse transcriptase polymerase chain reaction) involves assessing agreement of measurements obtained using the two techniques. Both bDNA and RT-PCR assays have lower limits of detection and thus new statistical methods are needed for assessing agreement between two left-censored variables. In this paper, we present maximum likelihood and generalized estimating equations approaches to evaluate agreement between two assays that are subject to lower limits of detection. The concordance correlation coefficient is used as an agreement index. The methodology is illustrated using HIV RNA assay data collected as part of a long-term HIV cohort study.

Sentinel lymph node biopsy in the management of cutaneous head and neck melanoma.

Sentinel lymph node biopsy has revolutionized the surgical management of primary malignant melanoma. Most series on sentinel lymph node mapping have concentrated on extremity and truncal melanomas. The head and neck region has a rich and unpredictable lymphatic system. The use of sentinel lymph node mapping in the management of head and neck melanoma is evaluated. The authors conducted a retrospective review of patients treated for clinical stage I and stage II malignant melanoma of the head and neck with dynamic lymphoscintigraphy and gamma probe-guided sentinel lymph node biopsy. One hundred thirty-two patients (99 male patients and 33 female patients) were identified. The primary melanoma sites were the scalp (n = 54), ear (n = 14), face (n = 37), and neck (n = 27). Primary tumor staging was as follows: T1, 11; T2, 38; T3, 39; and T4, 44. Dynamic lymphoscintigraphy visualized sentinel lymph nodes in 128 patients (97 percent). In 71 cases (55 percent), a single draining nodal basin was identified, and in 57 cases there were multiple draining nodal basins (two basins, 55; three basins, two). Sentinel lymph nodes were successfully identified in 176 of 186 nodal basins (95 percent). Positive sentinel lymph nodes were identified in 22 patients (17.6 percent). Sentinel lymph node positivity by tumor staging was as follows: T2, 10.8 percent; T3, 19.4 percent; and T4, 26.8 percent. Completion lymphadenectomy revealed residual disease in seven patients (33.3 percent). Sentinel lymph node mapping for head and neck melanoma can be performed with results comparable to those of other anatomical sites.

Expression of e-cadherin in high-risk breast cancer.

PURPOSE: E-cadherin expression is diverse, and differences in patient characteristics may produce variability in expression. Whereas some studies have indicated that downregulation of e-cadherin, associated with loss of cellular adhesiveness, was correlative with poor prognosis and metastasis, other studies have failed to confirm this. The present study uses a highly homogenous population of patients at high-risk for breast cancer, on the basis of ethnic and socio-economic status, to examine the relationship between e-cadherin and other prognostic markers in breast cancer. METHODS: Immunohistochemical staining was undertaken for estrogen (ER) and progesterone (PR) receptors, epidermal growth factor receptor 2 (Her-2), p53, vascular endothelial factor (VEGF), and hypoxia inducible factor 1alpha (HIF-1alpha) and the levels of these markers was compared to e-cadherin expression in a high-risk African-American patient population. RESULTS: E-cadherin expression persisted into the later stagers of the disease, and was strongly associated with Her-2 and HIF-1alpha expression, but not p53, ER/PR or VEGF. CONCLUSIONS: In contrast to other studies on heterogeneous populations, e-cadherin is preserved in aggressive tumors in this high-risk population. The ethnic and socio-economic risk stratification needs to be accounted for in studies correlating markers and prognosis.