Richard M. Single

Variability in Reexcision Following Breast Conservation Surgery

CONTEXT Health care reform calls for increasing physician accountability and transparency of outcomes. Partial mastectomy is the most commonly performed procedure for invasive breast cancer and often requires reexcision. Variability in reexcision might be reflective of the quality of care. OBJECTIVE To assess hospital and surgeon-specific variation in reexcision rates following partial mastectomy. DESIGN, SETTING, AND PATIENTS An observational study of breast surgery performed between 2003 and 2008 intended to evaluate variability in breast cancer surgical care outcomes and evaluate potential quality measures of breast cancer surgery. Women with invasive breast cancer undergoing partial mastectomy from 4 institutions were studied (1 university hospital [University of Vermont] and 3 large health plans [Kaiser Permanente Colorado, Group Health, and Marshfield Clinic]). Data were obtained from electronic medical records and chart abstraction of surgical, pathology, radiology, and outpatient records, including detailed surgical margin status. Logistic regression including surgeon-level random effects was used to identify predictors of reexcision. MAIN OUTCOME MEASURE Incidence of reexcision. RESULTS A total of 2206 women with 2220 invasive breast cancers underwent partial mastectomy and 509 patients (22.9%; 95% CI, 21.2%-24.7%) underwent reexcision (454 patients [89.2%; 95% CI, 86.5%-91.9%] had 1 reexcision, 48 [9.4%; 95% CI, 6.9%-12.0%] had 2 reexcisions, and 7 [1.4%; 95% CI, 0.4%-2.4%] had 3 reexcisions). Among all patients undergoing initial partial mastectomy, total mastectomy was performed in 190 patients (8.5%; 95% CI, 7.2%-9.5%). Reexcision rates for margin status following initial surgery were 85.9% (95% CI, 82.0%-89.8%) for initial positive margins, 47.9% (95% CI, 42.0%-53.9%) for less than 1.0 mm margins, 20.2% (95% CI, 15.3%-25.0%) for 1.0 to 1.9 mm margins, and 6.3% (95% CI, 3.2%-9.3%) for 2.0 to 2.9 mm margins. For patients with negative margins, reexcision rates varied widely among surgeons (range, 0%-70%; P = .003) and institutions (range, 1.7%-20.9%; P < .001). Reexcision rates were not associated with surgeon procedure volume after adjusting for case mix (P = .92). CONCLUSION Substantial surgeon and institutional variation were observed in reexcision following partial mastectomy in women with invasive breast cancer.

Surgical Resection of Primary Tumors in Patients Who Present With Stage IV Colorectal Cancer: An Analysis of Surveillance, Epidemiology, and End Results Data, 1988 to 2000

BackgroundSurgical resection of the primary tumor for patients who present with incurable stage IV colorectal cancer is controversial. National practice patterns have not been described. We evaluated the use of primary tumor resection in patients presenting with stage IV colorectal cancer.MethodsPatients with stage IV colorectal cancer diagnosed between 1988 and 2000 were selected from the Surveillance, Epidemiology, and End Results database. Patients undergoing primary tumor resection were analyzed on the basis of sex, race, year of diagnosis, and the anatomical site of the primary tumor. We compared the survival of resected and nonresected patients.ResultsA total of 17,658 (66%) of the 26,754 patients presenting with stage IV colorectal cancer underwent primary tumor resection. Patients with resected disease were more likely to be young (mean age of 67.1 vs. 70.3 years) and to have right-sided tumors (75.3%, 73.0%, and 45.6%, respectively, for right, left, and rectal; P < .001). In all age groups, patients undergoing resection had higher median and 1-year survival rates (colon: 11 vs. 2 months, 45% vs. 12%, P < .001; rectum: 16 vs. 6 months, 59% vs. 25%, P < .001) when compared with patients who did not undergo resection.ConclusionsMost patients who present with stage IV colorectal cancer undergo resection of the primary tumor. The proportion of patients undergoing resection depends on patient age and race and the anatomical location of the primary tumor. The degree to which case selection explains the treatment and survival differences observed is not known. Further investigation of the role of surgery in the management of incurable stage IV colorectal cancer is warranted.

Balancing selection and heterogeneity across the classical human leukocyte antigen loci: a meta-analytic review of 497 population studies

This paper presents a meta-analysis of high-resolution human leukocyte antigen (HLA) allele frequency data describing 497 population samples. Most of the datasets were compiled from studies published in eight journals from 1990 to 2007; additional datasets came from the International Histocompatibility Workshops and from the AlleleFrequencies.net database. In all, these data represent approximately 66,800 individuals from throughout the world, providing an opportunity to observe trends that may not have been evident at the time the data were originally analyzed, especially with regard to the relative importance of balancing selection among the HLA loci. Population genetic measures of allele frequency distributions were summarized across populations by locus and geographic region. A role for balancing selection maintaining much of HLA variation was confirmed. Further, the breadth of this meta-analysis allowed the ranking of the HLA loci, with DQA1 and HLA-C showing the strongest balancing selection and DPB1 being compatible with neutrality. Comparisons of the allelic spectra reported by studies since 1990 indicate that most of the HLA alleles identified since 2000 are very-low-frequency alleles. The literature-based allele-count data, as well as maps summarizing the geographic distributions for each allele, are available online.

Global diversity and evidence for coevolution of KIR and HLA.

The killer immunoglobulin-like receptor (KIR) gene cluster shows extensive genetic diversity, as do the HLA class I loci, which encode ligands for KIR molecules. We genotyped 1,642 individuals from 30 geographically distinct populations to examine population-level evidence for coevolution of these two functionally related but unlinked gene clusters. We observed strong negative correlations between the presence of activating KIR genes and their corresponding HLA ligand groups across populations, especially KIR3DS1 and its putative HLA-B Bw4-80I ligands (r = −0.66, P = 0.038). In contrast, we observed weak positive relationships between the various inhibitory KIR genes and their ligands. We observed a negative correlation between distance from East Africa and frequency of activating KIR genes and their corresponding ligands, suggesting a balance between selection on HLA and KIR loci. Most KIR-HLA genetic association studies indicate a primary influence of activating KIR-HLA genotypes in disease risk; concomitantly, activating receptor-ligand pairs in this study show the strongest signature of coevolution of these two complex genetic systems as compared with inhibitory receptor-ligand pairs.

Surface EMG electrodes do not accurately record from lumbar multifidus muscles

OBJECTIVE This study investigated whether electromyographic signals recorded from the skin surface overlying the multifidus muscles could be used to quantify their activity. DESIGN Comparison of electromyography signals recorded from electrodes on the back surface and from wire electrodes within four different slips of multifidus muscles of three human subjects performing isometric tasks that loaded the trunk from three different directions. BACKGROUND It has been suggested that suitably placed surface electrodes can be used to record activity in the deep multifidus muscles. METHODS We tested whether there was a stronger correlation and more consistent regression relationship between signals from electrodes overlying multifidus and longissimus muscles respectively than between signals from within multifidus and from the skin surface electrodes over multifidus. RESULTS The findings provided consistent evidence that the surface electrodes placed over multifidus muscles were more sensitive to the adjacent longissimus muscles than to the underlying multifidus muscles. The R(2) for surface versus intra-muscular comparisons was 0.64, while the average R(2) for surface-multifidus versus surface-longissimus comparisons was 0.80. Also, the magnitude of the regression coefficients was less variable between different tasks for the longissimus versus surface multifidus comparisons. CONCLUSIONS Accurate measurement of multifidus muscle activity requires intra-muscular electrodes. RELEVANCE Electromyography is the accepted technique to document the level of muscular activation, but its specificity to particular muscles depends on correct electrode placement. For multifidus, intra-muscular electrodes are required.

PyPop: a software framework for population genomics: analyzing large-scale multi-locus genotype data.

Software to analyze multi-locus genotype data for entire populations is useful for estimating haplotype frequencies, deviation from Hardy-Weinberg equilibrium and patterns of linkage disequilibrium. These statistical results are important to both those interested in human genome variation and disease predisposition as well as evolutionary genetics. As part of the 13th International Histocompatibility and Immunogenetics Working Group (IHWG), we have developed a software framework (PyPop). The primary novelty of this package is that it allows integration of statistics across large numbers of data-sets by heavily utilizing the XML file format and the R statistical package to view graphical output, while retaining the ability to inter-operate with existing software. Largely developed to address human population data, it can, however, be used for population based data for any organism. We tested our software on the data from the 13th IHWG which involved data sets from at least 50 laboratories each of up to 1000 individuals with 9 MHC loci (both class I and class II) and found that it scales to large numbers of data sets well.

E‐mentoring for social equity: review of research to inform program development

The advent of user‐friendly email programs and web browsers created possibilities for widespread use of e‐mentoring programs. In this review of the research, we presented the history of e‐mentoring programs and defined e‐mentoring and structured e‐mentoring programs, focusing on large‐scale e‐mentoring programs that addressed issues of social equity and educational advancement. The literature reviewed spanned from the mid‐1990s to the present and included journal articles, reports, and book chapters on implemented e‐mentoring programs. The literature indicates that e‐mentoring is not a panacea, neither is it an inexpensive alternative to face‐to‐face mentoring. E‐mentoring is an alternative mode that facilitates the expansion of mentoring opportunities. The research we reviewed supported that the benefits associated with e‐mentoring mirrored the benefits associated with mentoring: informational, psychosocial, and instrumental. In addition, research supports two additional benefits of e‐mentoring: the value of impartiality and inter‐organizational connections, which were facilitated by the use of electronic communications. Research conducted on the programmatic features associated with e‐mentoring programs identified training, coaching, and group e‐mentoring as features that enhanced participant involvement. Our goal in providing a review of the research at this stage in the development of e‐mentoring was to facilitate increased understanding of the current research to enhance future research and programs and to advance e‐mentoring as a field.

NSABP-32: Phase III, randomized trial comparing axillary resection with sentinal lymph node dissection: A description of the trial

The NSABP-32 trial is a randomized, phase III clinical trial to compare sentinel node (SN) resection to conventional axillary dissection in clinically node-negative breast cancer patients. The primary aims of the trial are to determine if removal of only SNs provides survival and regional control equivalent to those of axillary dissection, while diminishing the magnitude of surgically related side effects. In order to ensure consistency of the outcomes for this trial, a standardized method of SN surgery has been utilized for all cases. A secondary aim of the B32 trial is to evaluate whether patients with “occult” metastases in the SNs have worse survival. Accrual is taking place at 73 institutions in North America, and 217 surgeons are enrolling patients.

Laparoscopic approaches to resection of suspected gastric gastrointestinal stromal tumors based on tumor location

BackgroundSurgical resection of gastric gastrointestinal stromal tumor (GIST) should be optimized to achieve a negative pathologic surgical margin while limiting the extent of stomach volume loss. Careful identification of exact gastric tumor location using preoperative computed tomography (CT) scans and gastroscopy should allow for selection of a specific operative approach.MethodsThis retrospective case series involved 12 patients (7 men and 5 women; mean age, 60.5 years) with suspected gastric GIST undergoing tumor resection at Fletcher Allen Health Care, a university medical center, from January 2005 to August 2006. The main outcome measures were pathologic resection margins, operative time, estimated blood loss (EBL), morbidity, and duration of hospital stay.ResultsThe 12 patients were separated into three groups on the basis of tumor location as follows: type 1 (fundus/greater curvature, n = 5), type 2 (prepyloric/antrum, n = 3), and type 3 (lesser curvature/perigastroesophageal junction, n = 4). Preoperative imaging (CT scan and/or endoscopy) used to identify tumor location accurately predicted the operative approach before surgery for 11 of the12 patients. The surgical approach was selected solely by tumor location as follows: type 1 (laparoscopic partial gastrectomy [LPG]), type 2 (laparoscopic distal gastrectomy [LDG]), and type 3 (laparoscopic transgastric resection [LTG]). Nine patients had a final pathologic diagnosis of GIST. The average tumor size was 4.6 cm, but this did not influence procedure selection. Histologic margins were microscopically negative in all patients. The LPG and LTG approaches had similar outcomes in terms of estimated blood loss (EBL; 80 vs 100 ml) and hospital stay (3.4 vs 3.3 days; p = 0.0198), but LTG had longer operative times (236 vs 180 min). The LDG procedure had longer operative times, greater EBL, and a longer hospital stay. The operative morbidity was 17%, and there was no operative mortality.ConclusionThe selection of an operative technique for resection of gastric submucosal tumors can be based on preoperative identification of tumor location, for better definition of both the extent of gastric resection and the technical complexity of the laparoscopic procedure.

Breast cancer survival according to number of nodes removed.

Background:Results from randomized trials indicate a 5.4% survival advantage associated with axillary dissection. To gain insight on survival outcomes when less than an axillary dissection is performed, we performed a retrospective analysis to determine survival outcome for node-negative and node-positive breast cancer patients when a variable number of nodes were excised.Methods:The data analyzed in this paper are from the Surveillance, Epidemiology, and End Results (SEER) database, from which 72,102 patients were selected whose breast cancer had been diagnosed in 1988 or later and who were aged 40–79 years at diagnosis, had a single primary lesion, and had 0 to 3 positive lymph nodes. Cases were separated into age groups (40 to 49 and 50 to 79 years), and node-negative cases were separated from those with one to three positive nodes.Results:This analysis indicates that even when all regional lymph nodes are pathologically negative, the number of nodes removed is associated with survival. In the group of breast cancer patients who had one to three pathologically positive nodes, as with the node-negative group, the higher the number of nodes removed, the greater the survival. The hazard rate for death in the node-negative group was roughly 5% less for each additional five nodes removed. For the node-positive group, the hazard rate for death was between 8% and 9% less for each additional five nodes removed.Conclusions:This retrospective study supports the notion that removal of regional nodes, even when such nodes are interpreted as pathologically negative, is important for the long-term survival of breast cancer patients.