Xinhua Yu

Mediastinal Lymph Node Examination and Survival in Resected Early-Stage Non–Small-Cell Lung Cancer in the Surveillance, Epidemiology, and End Results Database

Background: Pathologic nodal stage is the key prognostic factor in resectable non–small-cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes a poor prognosis. Yet, some NSCLC resections exclude MLN examination. Methods: We analyzed U.S. Surveillance, Epidemiology, and End Results program data from 1998 to 2002 to quantify the long-term survival impact of failure to examine MLN in resected NSCLC. We used Kaplan–Meier methods to compare the unadjusted survival difference between patients with, and without, MLN examination, and Cox proportional hazards and competing risk models to serially adjust for the impact of risk factors on survival differences. Results: Sixty-two percent of patients with pathologic N0 or N1 NSCLC had no MLN examined. Overall 5-year survival rates were 52% for those with, versus 47% for those without, MLN examination; lung cancer-specific survival rates were 63% versus 58% respectively (p < 0.001); nonlung cancer mortality was identical between cohorts. Adjusting for potential confounders, MLN examination was associated with a 7% reduction in all-cause mortality (hazard ratio, 0.93; confidence interval, 0.88–0.97; p = 0.002), and 11% reduction in lung cancer-specific mortality (hazard ratio, 0.89; 95% confidence interval, 0.84–0.95; p < 0.001) rates. The excess risk in 1 year’s cohort of U.S. lung resections was 3150 lives over 5 years. Conclusions: Failure to examine MLN was a common practice in MLN-negative NSCLC resections, which significantly impaired long-term survival. Efforts to understand the etiology of this quality gap, and measures to eliminate it, are warranted.

Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer

PURPOSE Pathologic nodal stage affects prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. PATIENTS AND METHODS We performed a case-control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. RESULTS We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. CONCLUSION Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC.

Number of Lymph Nodes Associated With Maximal Reduction of Long-Term Mortality Risk in Pathologic Node-Negative Non–Small Cell Lung Cancer

BACKGROUND Forty-four percent of patients with pathologic node negative (pN0) non-small cell lung cancer (NSCLC) die within 5 years of curative-intent surgical procedures. Heterogeneity in pathologic nodal examination practice raises concerns about the accuracy of nodal staging in these patients. We hypothesized a reciprocal relationship between the number of lymph nodes examined and the probability of missed lymph node metastasis and sought to identify the number of lymph nodes associated with the lowest mortality risk in pN0 NSCLC. METHODS We analyzed resections for first primary pN0 NSCLC in the United States Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2009, with survival updated to December 31, 2009. RESULTS In 24,650 eligible patients, there was a significant sequential reduction in mortality risk with examination of more lymph nodes. The lowest mortality risk occurred in those with 18 to 21 lymph nodes examined. The hazard ratio for all-cause mortality was 0.65 and the 95% confidence interval (CI) was 0.57 to 0.73; for lung cancer-specific mortality, hazard ratio was 0.62 and CI was 0.53 to 0.73 (p<0.001 for both). The median number of lymph nodes examined was only 6. CONCLUSIONS Lymph node evaluation falls far short of optimal in patients with resected pN0 NSCLC, raising the odds of underestimation of long-term mortality risk and failure to identify candidates for postoperative adjuvant therapy. This represents a major quality gap for which corrective intervention is warranted.

Use of a Surgical Specimen-Collection Kit to Improve Mediastinal Lymph-Node Examination of Resectable Lung Cancer

Introduction: Pathologic examination of mediastinal lymph nodes (MLNs) after resection of non–small-cell lung cancer is critical in the determination of prognosis and postoperative management. Although systematic nodal dissection is recommended, the quality of pathologic lymph-node staging often falls short of recommendations in practice. We tested the feasibility of improving pathologic lymph-node staging of resectable non–small-cell lung cancer by using a prelabeled specimen-collection kit. Methods: Case-control study with comparison of 51 resections, using a special lymph-node collection kit, with 51 controls matched for surgeon, extent of resection, pathologist, and T category. Appropriate statistical methods were used for all comparisons. Results: The median number of MLNs examined increased from one in the control group, to six in the case group (p < 0.001). The percentage of resections attaining the National Comprehensive Cancer Network-recommended quality of MLN examination, and the proportion that would have been eligible for recent landmark postresection adjuvant therapy trials increased significantly (p < 0.001). The duration of surgery and postoperative complication rates were similar between cases and controls. Eighteen percent of kit cases had positive MLN, compared with 8% of controls. Conclusions: The use of a specialized specimen-collection kit for MLN examination was feasible, markedly improved MLN staging, and showed a trend toward increased detection of patients with MLN metastasis, with only a modest increase in duration of surgery, and no increase in perioperative morbidity, mortality, or hospital length of stay.

The impact of a novel lung gross dissection protocol on intrapulmonary lymph node retrieval from lung cancer resection specimens.

Although thorough pathologic nodal staging provides the greatest prognostic information in patients with potentially curable non-small cell lung cancer, N1 nodal metastasis is frequently missed. We tested the impact of corrective intervention with a novel pathology gross dissection protocol on intrapulmonary lymph node retrieval. This study is a retrospective review of consecutive lobectomy, or greater, lung resection specimens over a period of 15 months before and 15 months after training pathologists assistants on the novel dissection protocol. One hundred forty one specimens were examined before and 121 specimens after introduction of the novel dissection protocol. The median number of intrapulmonary lymph nodes retrieved increased from 2 to 5 (P<.0001), and the 75th to 100th percentile range of detected intrapulmonary lymph node metastasis increased from 0 to 5 to 0 to 17 (P=.0003). In multivariate analysis, the extent of resection, examination period (preintervention or postintervention), and pathologic N1 (vs N0) status were most strongly associated with a higher number of intrapulmonary lymph nodes examined. A novel pathology dissection protocol is a feasible and effective means of improving the retrieval of intrapulmonary lymph nodes for examination. Further studies to enhance dissemination and implementation of this novel pathology dissection protocol are warranted.

Computer modeling of lung cancer diagnosis-to-treatment process.

We introduce an example of a rigorous, quantitative method for quality improvement in lung cancer care-delivery. Computer process modeling methods are introduced for lung cancer diagnosis, staging and treatment selection process. Two types of process modeling techniques, discrete event simulation (DES) and analytical models, are briefly reviewed. Recent developments in DES are outlined and the necessary data and procedures to develop a DES model for lung cancer diagnosis, leading up to surgical treatment process are summarized. The analytical models include both Markov chain model and closed formulas. The Markov chain models with its application in healthcare are introduced and the approach to derive a lung cancer diagnosis process model is presented. Similarly, the procedure to derive closed formulas evaluating the diagnosis process performance is outlined. Finally, the pros and cons of these methods are discussed.

Birth Prevalence of Sickle Cell Trait and Sickle Cell Disease in Shelby County, TN

Accurate quantification of the regional burden of sickle cell disease (SCD) is vital to allocating health‐related resources. Shelby County, TN, which includes the city of Memphis and the regional pediatric SCD treatment center at St. Jude Childrens Research Hospital, is home to a large population of African Americans.

Distance from an Urban Sickle Cell Center and its Effects on Routine Healthcare Management and Rates of Hospitalization.

Abstract The St. Jude Children’s Research Hospital (St. Jude) comprehensive sickle cell center serves a 150 mile catchment radius around Memphis, TN, USA. Full travel expenses are provided for routine and acute care visits for sickle cell disease patients living ≥35 miles from St. Jude. We compared hospitalization rates to national estimates and assessed if driving distance was a barrier to sickle cell healthcare despite the travel reimbursement policy. We evaluated the associations between hospitalizations and routine clinic visits and distance from St. Jude using negative binomial models and we conducted bias analyses by Monte Carlo simulation. We followed 545 patients (2550 patient-years) aged ≤18 years with sickle cell disease (Hb SS only) from 2007 to 2012. The hospitalization rate per patient-year was 0.65 [95% CI (confidence interval): 0.62, 0.68), significantly lower than the national rate of 1.16 (95% CI: 1.14, 1.18). Children living <35 miles from St. Jude had 1.75 (95% CI: 1.41, 2.17) times the rate of hospitalization and 1.22 (95% CI: 1.07, 1.39) times the rate of clinic visits compared to those ≥35 miles. Bias analysis suggested that under-reporting could explain the observed difference in hospitalization rates if 30.0% of patients who lived ≥35 miles from the hospital under-reported six hospitalizations over 6 years. The hospitalization rate at St. Jude in children with sickle cell disease was lower than expected from national rates. Greater distance from the sickle cell center (>35 miles) was associated with decreased hospitalization rates, despite the travel allowances that are provided for those who live ≥35 miles from the hospital.

Measuring improvement in populations: implementing and evaluating successful change in lung cancer care

Improving quality of care in lung cancer, the leading cause of cancer death worldwide and in the United States, is a major public health challenge. Such improvement requires accurate and meaningful measurement of quality of care. Preliminary indicators have been derived from clinical practice guidelines and expert opinions, but there are few standard sets of quality of care measures for lung cancer in the United States or elsewhere. Research to develop validated evidence-based quality of care measures is critical in promoting population improvement initiatives in lung cancer. Furthermore, novel research designs beyond the traditional randomized controlled trials (RCTs) are needed for wide-scale applications of quality improvement and should extend into alternative designs such as quasi-experimental designs, rigorous observational studies, population modeling, and other pragmatic study designs. We discuss several study design options to aid the development of practical, actionable, and measurable quality standards for lung cancer care. We also provide examples of ongoing pragmatic studies for the dissemination and implementation of lung cancer quality improvement interventions in community settings.

Factors associated with residential mobility during pregnancy

ABSTRACT Our objective was to determine the factors associated with residential moving during pregnancy, as it may increase stress during pregnancy and affect birth outcomes. Data were obtained from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study. Participants were recruited from December 2006 to June 2011 and included 1,448 pregnant women. The average gestational age at enrollment was 23 weeks. The primary outcome of residential mobility was defined as any change in address during pregnancy. Multivariate regression was used to assess the adjusted associations of factors with residential mobility. Out of 1,448 participants, approximately 9 percent moved between baseline (enrollment) and delivery. After adjusting for covariates, mothers with lower educational attainment [less than high school (adjusted odds ratio [aOR] = 3.74, 95% confidence interval [CI] = 1.78, 7.85) and high school/technical school (aOR = 3.57, 95% CI = 2.01, 6.32) compared to college degree or higher], and shorter length of residence in neighborhood were more likely to have moved compared to other mothers. Length of residence was protective of mobility (aOR = 0.91, 95% CI = 0.86, 0.96 per year). Increased understanding of residential mobility during pregnancy may help improve the health of mothers and their children.