Abstract
Background
A small proportion of non–small cell lung cancers (NSCLCs) have been observed to spread to distant lymph nodes (N3) or metastasize (M1) or both, while the primary tumor is small ...(≤3 cm, T1). These small aggressive NSCLCs (SA-NSLSC) are important as they are clinically significant, may identify unique biologic pathways, and warrant aggressive follow-up and treatment. This study identifies factors associated with SA-NSCLC and attempts to validate a previous finding that women with a family history of lung cancer are at particularly elevated risk of SA-NSCLC.
Methods
This study used a case–case design within the National Cancer Institute’s National Lung Screening Trial (NLST) cohort. Case patients and “control” patients were selected based on TNM staging parameters. Case patients (n = 64) had T1 NSCLCs that were N3 or M1 or both, while “control” patients (n = 206) had T2 or T3, N0 to N2, and M0 NSCLCs. Univariate and multivariable logistic regression were used to identify factors associated with SA-NSCLC.
Results
In bootstrap bias–corrected multivariable logistic regression models, small aggressive adenocarcinomas were associated with a positive history of emphysema (odds ratio OR = 5.15, 95% confidence interval CI = 1.63 to 23.00) and the interaction of female sex and a positive family history of lung cancer (OR = 6.55, 95% CI = 1.06 to 50.80).
Conclusions
Emphysema may play a role in early lung cancer progression. Females with a family history of lung cancer are at increased risk of having small aggressive lung adenocarcinomas. These results validate previous findings and encourage research on the role of female hormones interacting with family history and genetic factors in lung carcinogenesis and progression.
BackgroundIn this study, we analyzed the clinical outcomes at a minimum of two years following reconstruction of the anterior cruciate ligament with use of a four-strand hamstring tendon autograft in ...patients who had presented with a symptomatic torn anterior cruciate ligament.MethodsOne hundred and twenty-two consecutive patients who had an isolated, symptomatic anterior tibial subluxation associated with rupture of the anterior cruciate ligament were treated with reconstruction of the anterior cruciate ligament with a four-strand autologous semitendinosus-gracilis tendon graft. One surgeon performed all of the operations. Prior to surgery and at the follow-up examination, physical findings and functional scores were recorded and knee radiographs were analyzed. Following surgery, a six-month rehabilitation regimen was implemented.ResultsEighty-five patients (70%) were available for follow-up, which included physical examination, scoring of function, KT-1000 arthrometric testing, and radiographs, at a mean of twenty-eight months. Seventy-six (89%) of the patients had negative Lachman and pivot shift tests. The mean Lysholm score improved from 55 points preoperatively to 91 points at the time of follow-up (p < 0.01). The mean Tegner score improved from 5 to 6 points (p < 0.01). Sixty-five patients had <3 mm of knee translation on arthrometric testing, but six patients with marked laxity were not tested. Three patients (4%) had a positive pivot shift test but had no history of additional trauma to the knee. Six patients (7%) had a traumatic rupture of the graft, occurring at a mean of 10.7 months postoperatively. Assessment of the follow-up radiographs demonstrated no evidence of progressive degenerative change compared with the appearance on the preoperative radiographs. However, tunnel expansion was noted in all patients. The tibial tunnel expanded a mean of 17% (range, 0% to 32%), and the femoral tunnel expanded a mean of 29% (range, 0% to 40%).ConclusionsReconstruction of the anterior cruciate ligament with use of a four-strand hamstring tendon autograft eliminated anterior tibial subluxation in 89% of patients who were examined at a minimum of two years postoperatively. The overall rate of failure was 11%. The functional knee scores were significantly increased at the time of follow-up, but these results did not correlate with the results of knee arthrometric testing.Level of EvidenceTherapeutic study, Level IV (case series no, or historical, control group). See Instructions to Authors for a complete description of levels of evidence.
Background: Some non–small cell lung cancers (NSCLC) progress to distant lymph nodes or metastasize while relatively small.
Such small aggressive NSCLCs (SA-NSCLC) are no longer resectable with ...curative intent, carry a grave prognosis, and may involve
unique biological pathways. This is a study of factors associated with SA-NSCLC.
Methods: A nested case-case study was embedded in the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer
Screening Trial. SA-NSCLC cases had stage T 1 , N 3 , and/or M 1 NSCLC ( n = 48) and non–SA-NSCLC cases had T 2 to T 3 , N 0 to N 2 , and M 0 NSCLC ( n = 329). Associations were assessed by multiple logistic regression.
Results: SA-NSCLCs were associated with younger age at diagnosis odds ratio (OR) ≥65 versus <65 , 0.44; 95% confidence interval (95% CI), 0.22-0.88, female gender, family history of lung cancer, and the interaction gender*family
history of lung cancer and were inversely associated with ibuprofen use (OR yes versus no , 0.29; 95% CI, 0.11-0.76). The ORs for associating gender (women versus men) with SA-NSCLC in those with and without a family
history of lung cancer were 11.76 (95% CI, 2.00-69.22) and 1.86 (95% CI, 0.88-3.96), respectively. These associations held
adjusted for histology and time from screening to diagnosis and when alternative controls were assessed.
Conclusion: SA-NSCLC was associated with female gender, especially in those with a family history of lung cancer. If these
exploratory findings, which are subject to bias, are validated as causal, elucidation of the genetic and female factors involved
may improve understanding of cancer progression and lead to preventions and therapies. Ibuprofen may inhibit lung cancer progression.
(Cancer Epidemiol Biomarkers Prev 2007;16(10):2082–9)
Abstract
Background: Lung cancer (LC) survivors in the U.S. are increasing in number, with 5-year survival rates improving by 26% over the past decade. Although LC survivors are at high risk of ...developing a second primary lung cancer (SPLC), risk factors for SPLC have not been established and the impact of tobacco smoking remains controversial. In this study, we examined risk factors for SPLC among participants in the Multiethnic Cohort (MEC) study, validated our findings with two epidemiologic cohorts–the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and the European Prospective Investigation into Cancer and Nutrition (EPIC)–and evaluated the impact of smoking cessation on SPLC risk.
Methods: We analyzed data from 7,299 initial primary lung cancer (IPLC) cases in MEC who were diagnosed from 1993-2017. Incident IPLC and SPLC were identified via linkage to SEER registries, with SPLC defined by Martini and Melamed criteria. Baseline smoking data were obtained at the time of enrollment (1993-1996) and updated with 10-year follow-up data close to IPLC diagnosis, if available. Fine-Gray regression was used to take into account competing risks and to evaluate the associations between risk factors and SPLC, adjusting for age at IPLC diagnosis and IPLC histology and stage. We conducted validation studies with PLCO (N=3,423 LC patients) and EPIC (N=4,605 LC patients) and evaluated the combined effects of risk factors from all three cohorts using meta-analysis.
Results: Among 7,299 MEC participants with IPLC, 167 (2.3%) developed a SPLC. Fine-Gray regression analyses identified several factors that were significantly associated with SPLC risk (P<0.05), which included smoking pack-years (HR 1.12 per 10 pack-years (PY); P=0.004) and smoking intensity (HR 1.21 per 10 cigarettes per day (CPD); P=0.017). Individuals who met the U.S. Preventative Services Task Force's (USPSTF) screening criteria (i.e., aged 55-80, smoked ≥30 PY, and ≤15 years since smoking cessation) at the time of IPLC had a 68% increase in SPLC risk (HR 1.68; P=0.001). Validation studies with PLCO and EPIC showed consistent results; the combined effects based on meta-analysis showed a HR 1.15 per 10 PY (Pmeta=0.022) for smoking pack-years, HR 1.18 per 10 CPD (Pmeta=6.0x10-4) for smoking intensity, and HR 1.70 (Pmeta = 1.9x10-5) for meeting the USPSTF criteria. Subset analysis of MEC participants (N=156) who were current smokers at baseline, had 10-year follow-up smoking data, and were diagnosed with IPLC between baseline and 10-year follow-up showed that smoking cessation was associated with a reduced risk of SPLC (HR=0.25; P=0.005).
Conclusions: Smoking is a risk factor for SPLC among LC patients and the USPSTF criteria can potentially aid in identifying those at high risk of SPLC. Smoking cessation may reduce SPLC risk after IPLC diagnosis. Further analysis is required to stratify SPLC risk based on comprehensive risk factors and identify LC survivors at high risk of SPLC for CT screening.
Citation Format: Jacqueline V. Aredo, Sophia J. Luo, Rebecca Gardner, Thomas P. Hickey, Thomas L. Riley, Lynne R. Wilkens, Loic Le Marchand, Christopher I. Amos, Rayjean J. Hung, Mattias Johansson, Iona Cheng, Heather A. Wakelee, Summer S. Han. Is smoking a risk factor for second primary lung cancer abstract. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2298.
Importance
Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former ...National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.
Objective
To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.
Design, Setting, and Participants
This cross-sectional study used carbon 11–labeled
N
,
N
-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo1,5-
a
pyrimidine-3-acetamide positron emission tomography (
11
CDPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023.
Main outcomes and measures
Regional
11
CDPA-713 total distribution volume from
11
CDPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains.
Results
This study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized β coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52;
P
< .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference MD, −0.70; 95% CI, −1.14 to −0.25;
P
= .003) and memory (MD, −0.77; 95% CI, −1.24 to −0.30;
P
= .002), with no correlation between total gray matter TSPO and these cognitive domains.
Conclusions and relevance
In this cross-sectional study using
11
CDPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal
11
CDPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.
To evaluate positive predictive values of CA 125 or transvaginal ultrasonography screening for ovarian cancer according to family history of breast or ovarian cancer.
In the screening arm of a ...randomized controlled trial of screening compared with usual care, 28,460 women with family history data received baseline and annual CA 125 and transvaginal ultrasonography examinations. We analyzed CA 125 and transvaginal ultrasonography results from the first four rounds of screening. We classified women as average (n=22,687), moderate (n=2,572), or high (n=2,163) risk based on family history, or high risk due to a personal history of breast cancer (n=1,038). Cancers were identified by active follow-up of women with abnormal screening results and annual questionnaires. We calculated positive predictive values for screening combinations.
Similar proportions (4.8-5.0%) of women in each group had abnormal screening results. Higher-risk women were more likely than lower-risk women to undergo biopsy after a positive screen. Screening identified 43 invasive ovarian cancers. The positive predictive values for abnormal screening results were 0.7% in average-risk, 1.3% in moderate-risk, and 1.6% in high-risk groups; one ovarian cancer occurred among the breast cancer survivors. The positive predictive values for postbaseline abnormal screening results were also higher in the higher-risk groups. The positive predictive values did not significantly differ across risk groups.
Probabilities of abnormal annual CA 125 and transvaginal ultrasonography screens were similar across groups based on family history of breast or ovarian cancer. However, ovarian cancer was more likely to be diagnosed after an abnormal screening result among women at higher family history-based risk than among women at lower risk.
I.
Postoperative loss of knee motion is a well-recognized phenomenon. This paper reports our results with open debridement and
soft tissue release as a salvage procedure in the treatment of patients ...with severe arthrofibrosis on whom arthroscopic surgical
techniques had failed. Eight knees (eight patients) were identified retrospectively. There were four men and four women; mean
age was 29 years. All had severely restricted motion with extensive intraarticular and periarticular fibrosis. Range of motion
averaged 62.5° preoperatively (flexion 81°, loss of extension 18.8°). Patients underwent open debridement and soft tissue
release to restore motion. There were no complications. Motion improved to an average of 124° after surgery. Average flexion
improved from 81° to 125°. Loss of extension improved from 18.8° to 1.25°. Functional outcome was good, with Lysholm II scores
averaging 79. Patient satisfaction was high. There was a high incidence of patellofemoral arthritis at follow-up. Furthermore,
the patellar tendon shortened approximately 6 mm over time. While we do not advocate open debridement and soft tissue release
as a first-line treatment for arthrofibrosis, we do conclude that it can be effective as a salvage procedure to restore motion
in the profoundly arthrofibrotic knee.
There exists a group of patients who are difficult to manage because they have both anterior knee instability secondary to
anterior cruciate ligament deficiency and unilateral degenerative joint ...disease. A large majority of these patients report
a history of previous meniscal injury or meniscectomy after knee trauma at a relatively young age. Active patients who report
symptomatic knee instability or pain associated with athletics or activities of daily living after conservative treatment
may be indicated for surgery. Current endoscopic methods of anterior cruciate ligament reconstruction result in low patient
morbidity, the elimination of anterior knee instability, and a timely return of function. Osteotomies about the knee joint
are an effective means of treating unicompartmental knee arthrosis. Long-term studies have demonstrated that knee osteotomy
is a good surgical option for patients with unicompartmental arthritis who are considered too young for total knee arthroplasty.
We describe a comprehensive treatment approach to the patient with anterior cruciate ligament deficiency and isolated medial
or lateral osteoarthritis. An assessment of pain symptoms, instability symptoms, and lower extremity alignment is used to
formulate a treatment plan.
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