Using an Electronic Perioperative Documentation Tool to Identify Returns to Operating Room (ROR) in a Tertiary Care Academic Medical Center.

BACKGROUND: The metric "Unplanned returns to operating room (ROR)" is being tracked in surgical quality dashboards; 70% of unplanned RORs may be related to surgical complications. With increasing regionalization of trauma and complex surgical care at tertiary care academic centers, it is unclear if a simple ROR metric is a valid assessment of surgical quality at such centers. METHOD: A real-time electronic tool was used to identify all RORs-planned and unplanned-in a high-volume, high-complexity academic surgical practice at Mayo Clinic-Rochester within 45 days of the index operation. Analysis by ROR type and indication was performed. RESULTS: During the analysis period (June 2014-February 2015) 44,031 operations were performed, with 5,552 subsequent RORs (13%). Of all RORs, 51% (n = 2,818) were planned staged returns, 29% (n = 1,589) were unrelated, 15% (n = 830) were unplanned and 6% (n = 315) were planned because of previous complications. Overall, unplanned reoperations were uncommon (n = 830, 2% of all operations). The most common indications for unplanned RORs included "other" (32%, n = 266), bleeding related (24%, n = 198) and wound complications (20%, n = 166). CONCLUSION: In a high-volume, high-complexity academic surgical practice, RORs occurred after 13% of cases. Unplanned returns were infrequent and usually were associated with complications; most RORs were planned staged or unrelated returns. A simple ROR metric that does not consider planned/unrelated returns is likely not a valid surgical quality measure. Electronic tools designed specifically to identify in real-time RORs, associated indication, and clinical validation should provide more reliable data for public reporting and quality improvement efforts.

Preoperative gabapentin for acute post-thoracotomy analgesia: a randomized, double-blinded, active placebo-controlled study.

BACKGROUND: The role of preoperative gabapentin in postoperative pain management is not clear, particularly in patients receiving regional blockade. Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain. We examined the effect of preoperative gabapentin in thoracotomy patients. METHODS: Adults undergoing elective thoracotomy were enrolled in this prospective, randomized, double-blinded, placebo-controlled study, and randomly assigned to receive 600 mg gabapentin or active placebo (12.5 mg diphenhydramine) orally within 2 hours preoperatively. Standardized management included thoracic epidural infusion, intravenous patient-controlled opioid analgesia, acetaminophen and ketorolac. Pain scores, opioid use and side effects were recorded for 48 hours. Pain was also assessed at 3 months. RESULTS: One hundred twenty patients (63 placebo and 57 gabapentin) were studied. Pain scores did not significantly differ at any time point (P = 0.53). Parenteral and oral opioid consumption was not significantly different between groups on postoperative day 1 or 2 (P > 0.05 in both cases). The frequency of side effects such as nausea and vomiting or respiratory depression was not significantly different between groups, but gabapentin was associated with decreased frequency of pruritus requiring nalbuphine (14% gabapentin vs. 43% control group, P < 0.001). The frequency of patients experiencing pain at 3 months post-thoracotomy was also comparable between groups (70% gabapentin vs. 66% placebo group, P = 0.72). CONCLUSIONS: A single preoperative oral dose of gabapentin (600 mg) did not reduce pain scores or opioid consumption following elective thoracotomy, and did not confer any analgesic benefit in the setting of effective multimodal analgesia that included thoracic epidural infusion.

Chasing zero: the drive to eliminate surgical site infections.

OBJECTIVES: It is estimated that healthcare associated infections (HAI) account for 1.7 million infections and 99,000 associated deaths each year, with annual direct medical costs of up to $45 billion. Surgical Site Infections (SSI) account for 17% of HAIs, an estimated annual cost of $3.5 to 10 billion for our country alone. This project was designed to pursue elimination of SSIs and document results. METHODS: Starting in 2009 a program to eliminate SSIs was undertaken at a nationally recognized academic health center. Interventions already outlined by CMS and IHI were utilized, along with additional interventions based on literature showing relationships with SSI reduction and best practices. Rapid deployment of multiple interventions (SSI Bundle) was undertaken. Tactics included standardized order sets, a centralized preoperative evaluation (POE) clinic, high compliance with intraoperative interventions, and widespread monthly reporting of compliance and results. Data from 2008 to 2010 were collected and analyzed. RESULTS: Between May 1, 2008 and June 30, 2010, all patients with Class I and Class II wounds were tracked for SSIs. Baseline data (May-June 2008) was obtained showing a Class I surgical site infection rate of 1.78%, Class II of 2.82% (total surgical volume: 4160 cases). As of the second quarter 2010, those rates have dropped to 0.51% and 1.44%, respectively (P < 0.001 and P = 0.013; total surgical cases: 2826). This represents a 57% decrease in the SSI rate with an estimated institution specific cost savings of nearly $1 million during the study period. CONCLUSION: Committed leadership, aggressive assurance of high compliance with multiple known interventions (SSI Bundle), transparency to achieve high levels of staff engagement, and centralization of critical surgical activities result in significant declines in SSIs with resulting substantial cost savings.

Getting the right training and job.

The authors discuss the factors to be considered in selecting locations in which to train and to practice, and in conducting successful interviews and site visits. The advantages and disadvantages of different types of surgical practice (ie, solo vs group) are also reviewed, as are issues surrounding negotiations related to contracts, benefits, and covenants.

Using a data-matrix-coded sponge counting system across a surgical practice: impact after 18 months.

BACKGROUND: Retained surgical items (RSIs), most commonly sponges, are infrequent. Yet despite sponge-counting standards, failure to maintain an accurate count is a common error. To improve counting performance, technology solutions have been developed. A data-matrix-coded sponge (DMS) system was evaluated and implemented in a high-volume academic surgical practice at Mayo Clinic Rochester (MCR). The primary end point was prevention of sponge RSIs after 18 months. METHODS: Two trials were conducted before implementation. A randomized-controlled trial assessed the system's function, efficiency, and ergonomics. The second, larger trial was conducted to validate the prior findings and test product improvements. After the trials, the system was implemented in all 128 operating/procedure rooms across the MCR campus on February 2, 2009. The institutionwide implementation was intended to avoid the possibility of having standard unmarked sponges and DMSs in the operating room suite concurrently. RESULTS: Before implementation, a retained sponge occurred on average every 64 days. Between February 2009 and July 2010, 87,404 procedures were performed, and 1,862,373 DMSs were used without an RSI (p < .001). After four cases, the average time to count a DMS decreased from 11 to 4 seconds. Total sponge counting time/operation increased without any increase in overall operative time. CONCLUSIONS: After 18 months, a DMS system eliminated sponge RSIs from a high-volume surgical practice. The DMS system caused no work-flow disruption or increases in case duration. Staff satisfaction was acceptable, with a high degree of trust in the system. The DMS system is a reliable and cost-effective technology that improves patient safety.

Genetic variants and risk of lung cancer in never smokers: a genome-wide association study.

BACKGROUND: Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers. METHODS: We did a four-stage investigation. First, a genome-wide association study of single nucleotide polymorphisms (SNPs) was done with 754 never smokers (377 matched case-control pairs at Mayo Clinic, Rochester, MN, USA). Second, the top candidate SNPs from the first study were validated in two independent studies among 735 (MD Anderson Cancer Center, Houston, TX, USA) and 253 (Harvard University, Boston, MA, USA) never smokers. Third, further replication of the top SNP was done in 530 never smokers (UCLA, Los Angeles, CA, USA). Fourth, expression quantitative trait loci (eQTL) and gene-expression differences were analysed to further elucidate the causal relation between the validated SNPs and the risk of lung cancer in never smokers. FINDINGS: 44 top candidate SNPs were identified that might alter the risk of lung cancer in never smokers. rs2352028 at chromosome 13q31.3 was subsequently replicated with an additive genetic model in the four independent studies, with a combined odds ratio of 1.46 (95% CI 1.26-1.70, p=5.94x10(-6)). A cis eQTL analysis showed there was a strong correlation between genotypes of the replicated SNPs and the transcription level of the gene GPC5 in normal lung tissues (p=1.96x10(-4)), with the high-risk allele linked with lower expression. Additionally, the transcription level of GPC5 in normal lung tissue was twice that detected in matched lung adenocarcinoma tissue (p=6.75x10(-11)). INTERPRETATION: Genetic variants at 13q31.3 alter the expression of GPC5, and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute to the development of lung cancer in never smokers. FUNDING: US National Institutes of Health; Mayo Foundation.

Marital status and quality of life in patients with esophageal cancer or Barrett's esophagus: the mayo clinic esophageal adenocarcinoma and Barrett's esophagus registry study.

BACKGROUND: Patients with esophageal carcinoma (EC) report deficits in quality of life (QOL), depending on the extent of malignant disease and the goals of treatment at the time of QOL measurement. AIMS: To quantify the association of marital status and changes in QOL over time in patients with EC and patients with Barrett's esophagus (BE). METHODS: Eligible patients in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry completed QOL assessments at baseline and approximately 1 year later. QOL was determined with a ten-point linear analog self-assessment scale evaluating overall QOL and 12 subscales. RESULTS: Overall, 489 BE patients and 212 EC patients were evaluated. Married EC patients reported higher baseline QOL in legal concerns (8.1 vs. 7.1; p = .04) and friend and family support (9.3 vs. 8.4; p = .02) than single EC patients. Over time, married EC patients had a decrease in pain frequency QOL compared to single EC patients (-0.9 vs. +0.6; p = .02), with other QOL measures being stable. Married BE patients showed higher social activity QOL at baseline than single BE patients (7.5 vs. 6.9; p = .02); QOL was stable over time between the marital status groups. CONCLUSIONS: Minor, but statistically significant, changes were reported regarding QOL in two categories at baseline and over time among married and single patients with EC. Minor differences may be present between married and single EC patients regarding spiritual QOL at baseline and in overall physical well-being QOL at baseline and over time, although these differences did not reach statistical significance.

Entrapment of a nasopharyngeal temperature probe: an unusual complication during an apparently uneventful elective revision laparoscopic Nissen fundoplication.

We report the first case of nasopharyngeal temperature probe entrapment during an apparently uneventful elective revision laparoscopic Nissen fundoplication that precipitated a continuous quality improvement project at our institution. We describe changes in our clinical practice that resulted from this occurrence and envision these modifications will have a positive influence on patient care.

A multidisciplinary team approach to retained foreign objects.

BACKGROUND: Retained foreign objects (RFOs) after surgical procedures are an infrequent but potentially devastating medical error. The Mayo Clinic, Rochester (MCR), undertook a quality improvement program to reduce the incidence of surgical RFOs. METHOD: A multidisciplinary, multiphase approach was initiated in 2005. The effort, led by surgical, nursing, and administrative institutional leaders, was divided into three phases. The first phase included a defect analysis and policy review. A detailed analysis of all RFOs (both true and near misses) was undertaken to identify patterns of failures unique to our institution and operating room culture. Simultaneously, a review of all relevant institutional policies was performed, with comprehensive revisions focusing on increased clarity and inter- and intrapolicy consistency. The second phase involved increasing awareness and communication among all operating room personnel, including surgeons, residents, nursing, and allied health staff. The education program included all-staff conferences, team training, simulation videos, and daily education reminders and in-room audits. Finally, a monitoring and control phase involved rapid leadership response teams to any events, enhanced staff communication, and policy reviews. RESULTS: When the program started, MCR was averaging a surgical RFO every 16 days. After the intervention, the average interval between RFO events increased to 69 days, a level of performance that has been sustained for more than two years. DISCUSSION: MCR experienced a significant and sustained reduction in the incidents of RFOs, attributed to the multidisciplinary nature of the initiative, the active engagement of institutional leadership, and use of the principles of enhanced communication between operating room staff members to improve operating room situational awareness.

The role of positron emission tomography in the management of non-small cell lung cancer.

The potential use of positron emission tomography (PET) imaging in patients with non-small cell lung cancer (NSCLC) is broadly divided into 5 categories: management of solitary pulmonary nodule, mediastinal lymph node evaluation, detection of metastases, evaluation of response to chemoradiation and detection of recurrence. The purpose of this review is to discuss the current clinical applications of (18)F-fluorodeoxyglucose PET in patients with NSCLC and to discuss future applications and developments of this technology.

Nomogram prediction of overall survival for patients with non-small-cell lung cancer incorporating pretreatment peripheral blood markers.

OBJECTIVES: The objective of this study is to build a novel prognostic nomogram in non-small-cell lung cancer (NSCLC) incorporating pre-treatment peripheral blood markers beyond known pathoclinical predictors. METHODS: We analysed 7158 patients with NSCLC diagnosed between 1 January 1997 and 31 December 2012 from a single institution with a uniform medical record and routine follow-up information. Besides common clinicopathological factors, we investigated the prognostic value of the neutrophil to lymphocyte ratio, monocytes and haemoglobin level in peripheral blood before treatment. Patients were randomly assigned to training (4772 patients, 66.7%) or validation cohorts (2386 patients, 33.3%). Cox proportional hazards models determined the effects of multiple factors on overall survival (OS). A nomogram was developed to predict median survival and 1-, 3-, 5- and 10-year OS for NSCLC. The performance of the nomogram was assessed by a concordance index and calibration curve. RESULTS: In the training cohort, the multivariate Cox model identified the neutrophil to lymphocyte ratio, monocytes and haemoglobin level before treatment as significant prognostic factors for OS independent of patient age, gender, smoking history of intensity and cessation, performance status, disease stage, tumour cell type and differentiation grade and therapies. All the significant prognostic variables were incorporated into a nomogram. In the validation cohort, the nomogram showed notable accuracy in predicting OS, with a concordance index of 0.81, and was well calibrated for predictions of OS. CONCLUSIONS: The proposed nomogram incorporating peripheral blood markers and known prognostic factors could accurately predict individualized survival probability of patients with NSCLC. It could be used in treatment planning and stratification in clinical trials.

The influence of transabdominal gastroplasty: early outcomes of hiatal hernia repair.

OBJECTIVE: The aim of our study was to review our experience with transabdominal gastroplasty to determine the safety and short-term efficacy of the procedure. METHODS: Retrospective review of all patients that underwent transabdominal hiatal hernia repair with concurrent gastroplasty for shortened esophagus between October 1999 and May 2004. RESULTS: There were 63 patients, 27 men and 36 women. Median age was 68 years. The hiatal hernia was classified as type-I in 6 patients, type-II in 10, type-III in 43, and type-IV in 4. The operative approach was laparoscopic in 44 patients and laparotomy in 19. A Nissen fundoplication was performed in 62 patients and a Toupet fundoplication in 1. Wedge gastroplasty was performed in 47 patients and modified Collis gastroplasty in 16. Median hospitalization was 3 days (range, 2-10). Intraoperative complications occurred in 11 patients (17%). One laparoscopic approach (2%) was converted to laparotomy. Postoperative complications occurred in 12 patients (19%), there were no operative deaths. Median follow-up was 12 months (range, 0 to 64). One patient (2%) was found to have a recurrent hiatal hernia diagnosed 14 months, postoperatively. Functional results were excellent in 41 (68%), good in 6 (10%), fair in 12 (20%), and poor in 1 (2%). CONCLUSION: Transabdominal gastroplasty can be performed safely, with good functional results and a low incidence of recurrent herniation during the short-term follow-up period.

Lung cancer in octogenarians: factors affecting long-term survival following resection.

OBJECTIVE: To identify factors associated with long-term survival following pulmonary resection for lung cancer in patients 80 years of age or older. METHODS: The medical records of all patients >or=80 years, who underwent pulmonary resection for lung cancer from 1985 to 2002, were reviewed. RESULTS: There were 294 patients (192 men, 102 women). Median age was 82 years (range 80-94 years). Overall 1-, 2-, and 5-year survival was 80%, 62%, and 34%, respectively. Histologic subtype, diabetes, renal insufficiency, prior myocardial infarction, congestive heart failure or stroke were not significantly associated with differences in 5-year survival. Female gender was associated with increased survival (36.2% vs 32.7% at 5 years, p=0.04). Extent of preoperative forced expiratory volume in 1s (FEV1) limitation did not influence survival. However, there were no 5-year survivors amongst patients with dyspnea as their presenting chief complaint, whereas there was a 35% 5-year survival in patients presenting without dyspnea (p<0.001). Five-year survival by pathologic stage was IA, 48%; IB, 39%; IIA, 17%; IIB, 23%; IIIA, 9%; and IIIB, 0% (p<0.001). Five-year survival of patients undergoing a lobectomy was 42% versus 11% for pneumonectomy (p<0.001). CONCLUSIONS: Meaningful long-term survival is obtainable in elderly patients undergoing surgical resection for lung cancer. Careful patient evaluation and selection is necessary to identify patients who will benefit most from resection. Shorter survival was observed in male patients and those presenting with dyspnea. As could be expected, survival was also dependent on extent of resection and initial pathologic stage.

The role of pulmonary resection in small cell lung cancer.

OBJECTIVE: To analyze the outcome of surgical resection for patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: We identified all patients who underwent thoracotomy for SCLC at our institution from January 1985 to July 2002. All patients were staged using the American Joint Committee on Cancer TNM system. RESULTS: The median age of the 77 patients (44 men and 33 women) was 65 years (range, 35-85 years). Operations performed included thoracotomy with biopsy of hilar mass in 10 patients, wedge excision in 30 (6 with talc pleurodesis), segmentectomy in 4, lobectomy in 28, bilobectomy in 3, and pneumonectomy in 2. Mediastinal lymphadenectomy was performed in 50 patients and lymph node sampling in 19. Postoperative therapy Included chemotherapy alone in 20 patients, radiation therapy in 3, and combined chemotherapy and radiation therapy in 40. Median tumor diameter was 4 cm (range, 1.0-10.0 cm). Postsurgical tumor stage was IA in 7 patients, IB in 11, IIA in 8, IIB in 7, IIIA in 30, IIIB in 10, and IV in 4. A total of 19 patients (25%) had complications: atrial arrhythmia in 7 patients, pneumonia in 6, prolonged air leak in 3, and myocardial infarction, postoperative bleeding, and cerebrovascular accident in 1 each. Operative mortality was 3% (2/77). Follow-up ranged from 4 days to 170 months (median, 19 months). At last follow-up, 20 patients were alive. The estimated overall 5-year survival was 27% when excluding the 10 patients who underwent a biopsy without additional surgery. Five-year survival for stage I and II combined (n=33) was 38% compared with only 16% for stage III and IV combined (n=34) (P=.02). Overall median survival was 24 months; median survival for patients who underwent curative surgery was 25 months compared with 16 months for those who had a palliative procedure (P=.34). CONCLUSION: Pulmonary resection in patients with stage I or stage II SCLC is safe with low mortality and morbidity. Curative resection is associated with long-term survival in early stage SCLC in some patients and should be considered in selected patients.

Impact of prognostic factors on clinical outcome after resection of colorectal pulmonary metastases.

Colorectal cancer is the second leading cause of cancer-related deaths in Western countries. Approximately 35% of patients will have metastatic disease at diagnosis, and an additional 25% of patients with resected stage II/III disease will develop recurrence. In approximately 30% of patients, metastatic disease will be restricted to a single organ, with the liver and lungs accounting for the majority of single organ-site metastases. In recent years, aggressive surgical resection of pulmonary metastases has become increasingly common with the recognition that this offers the best chance of long-term cure despite recent chemotherapeutic advances. Unfortunately, relapse after pulmonary resection remains approximately 70% despite advances in imaging and surgical technique. This review examines prognostic factors that influence survival after resection and repeat resection of pulmonary colorectal metastases and examines the impact of lymph node metastases, chemotherapy, and hepatic metastases on outcome. Pathologic markers that might determine outcome and current literature, which consists mainly of retrospective institutional reports, is reviewed.

External validation of the Ferguson pulmonary risk score for predicting major pulmonary complications after oesophagectomy†.

OBJECTIVES: Pulmonary complications remain a frequent cause of morbidity in patients undergoing oesophagectomy. Risk screening tools assist in patient stratification. Ferguson proposed a risk score system to predict major pulmonary complications after oesophagectomy. Our objective was to externally validate this risk score system. METHODS: We analysed our institutional database for patients undergoing oesophagectomy for cancer from August 2009 to December 2012. We analysed patients who had complete documentation of variables used in the Ferguson risk score calculation: forced expiratory volume in the 1 s, diffusion capacity of the lung for carbon monoxide, performance status and age. One hundred and thirty-six patients qualified for analysis in the validation study. Outcome variables measured included major pulmonary complications, defined as need for reintubation for respiratory failure and pneumonia. The risk score was then calculated for each individual based on the model. Incidence of major pulmonary events was assessed in the five risk class groupings to assess the discriminative ability of the Ferguson score. RESULTS: Major pulmonary complications occurred in 35% of patients (47/136). Overall mortality was 6% (8/136). Patients were grouped into five risk categories according to their Ferguson pulmonary risk score: 0-2, 8 patients (6%); 3-4, 24 patients (18%); 5-6, 49 patients (36%); 29 patients (21%); 9-14, 26 patients (19%). The incidence of major pulmonary complications in these categories was 0, 17, 20, 41 and 77%, respectively. The accuracy of the risk score system for predicting major pulmonary complications was 76% (P < 0.0001). CONCLUSIONS: This pulmonary risk scoring system is a reliable instrument to be used during the preoperative phase to differentiate patients who may be at higher risk for pulmonary complications after oesophagectomy. These data can assist in patient selection, and in patient education/informed consent and can guide postoperative management.

Selective management of intrathoracic anastomotic leak after esophagectomy.

OBJECTIVE: We sought to analyze our experience with management of intrathoracic anastomotic leak after esophagectomy. METHODS: All patients who had intrathoracic anastomotic leaks after esophagectomy were reviewed. Management and factors affecting outcome were analyzed. RESULTS: From March 1993 through February 2003, 761 patients had esophagectomy with intrathoracic anastomosis at our institution. Forty-eight (6.3%) patients had an anastomotic leak; one refused authorization to review his medical record and was excluded from further analysis. Twenty-four (51.1%) patients had a contained leak. Twenty-seven (57.4%) patients were managed nonoperatively. Twenty (42.6%) patients required surgical intervention that included primary anastomotic repair in 14 patients, reinforcement of the anastomosis with viable tissue in 6 patients, and esophageal diversion in 2 patients. A single reoperation was done in 15 patients, and 5 patients had 2 reoperations. Median hospitalization in the reoperative group was 31 days (range, 15-97 days) and 20 days (range, 10-42 days) in the nonoperative group ( P = .0037). Four (8.5%) patients died. Cause of death was sepsis in 2 patients and multiorgan failure and myocardial infarction in 1 patient each. At follow-up (median, 8 months; range, 1-120 months), 10 (58.8%) patients in the reoperative group were eating a normal diet and 5 (29.4%) patients required at least one dilatation compared with 20 (76.9%) patients in the nonoperative group who were eating a normal diet and 9 (34.6%) who required at least one dilatation. A noncontained leak had an adverse effect on long-term survival ( P = .04). CONCLUSION: Intrathoracic anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Contained leaks often can be managed nonoperatively. When surgical management is required, esophagogastric continuity can often be maintained in the majority of patients. Long-term functional results are satisfactory and similar in both the reoperative and nonoperative groups. However, a noncontained leak adversely affected long-term survival.

Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003.

STUDY OBJECTIVES: To improve the current understanding of the etiology and natural history of primary lung cancer, we need to study the dynamic changes of clinical presentation and prognosis among a large number of patients with newly diagnosed lung cancer. In this report, we present the clinical features and survival rates up to 5 years of a patient cohort. DESIGN: We identified 5,628 primary lung cancer patients between 1997 and 2002 and followed them through 2003 using multiple, complementary resources. MEASUREMENTS AND RESULTS: Of the 5,628 patients, 58% were men with a mean age at lung cancer diagnosis of 66 years, and 42% were women with a mean age at diagnosis of 64 years. Ten percent were < 50 years, and 8% were > 80 years at diagnosis. A tobacco smoking history was present in 89% of patients, and 40% were smoking at the time of diagnosis. The estimated overall 5-year survival rates of patients with non-small cell lung cancer (NSCLC) by disease stage was as follows: IA, 66%; IB, 53%; IIA, 42%; IIB, 36%; IIIA, 10%; IIIB, 12%; and IV, 4%. The 5-year survival rate of patients with small cell lung cancer was 22% for limited disease and 1% for extensive disease. Approximately 50% of all patients are participants in one or more research studies, and nearly 75% of these patients have donated biological specimens for research. CONCLUSION: The survival rate of this cohort of lung cancer patients was slightly improved compared with earlier reports, particularly for patients with low-stage NSCLC. Our patient and biospecimen resource has enabled us to obtain timely results from clinical and translational research of lung cancer.

Alpha1-antitrypsin and neutrophil elastase imbalance and lung cancer risk.

OBJECTIVE: Imbalance between alpha(1)-antitrypsin and neutrophil elastase is an underlying cause of lung tissue damage that may create a favorable host environment for carcinogenesis. We conducted a case-control study to investigate whether genetic variations indicative of alpha(1)-antitrypsin deficiency (A1ATD) or an excess of neutrophil elastase modify lung cancer risk DESIGN: The case patients were 305 consecutively identified primary lung cancer patients, and the control subjects were 338 community residents. Protease inhibitor-1 (PI1), encoding alpha(1)-antitrypsin, was typed by an isoelectric focusing assay. Neutrophil elastase-2 (ELA2), encoding neutrophil elastase, was typed by two single-nucleotide polymorphism sites. Multivariable logistic regression models tested the independent and interactive effects of PI1, ELA2, tobacco smoke exposure, COPD, and family history of lung cancer RESULTS: Sex and ethnicity were comparable between case patients and control subjects, but case patients were more likely to be smokers, and to have a history of COPD, environmental tobacco smoke exposure, and a positive family history of lung cancer. Haplotype analysis indicated an overall strong association between the two ELA2 markers and lung cancer risk. Our best-fitting model showed significant and independent effects of the PI1-deficient allele (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4 to 3.0) and the ELA2 T-G haplotype (OR, 4.1; 95% CI, 1.9 to 8.9) on lung cancer risk, and an increased risk (OR, 2.6; 95% CI, 2.4 to 2.8) for individuals carrying both a PI1-deficient allele and a G-G haplotype CONCLUSIONS: Genotypes indicative of A1ATD and/or an excess of neutrophil elastase are significantly associated with lung cancer risk. Our findings may provide opportunities to better understand the mechanisms of lung cancer development and risk reduction.