Scaling a Hydraulic Motor for Minimally Invasive Medical Devices.

Aligned with the medical device industry's trend of miniaturization, academic and commercial researchers are constantly attempting to reduce device sizes. Many applications require miniature actuators (2 mm range) to perform mechanical work; however, biocompatible micromotors are not readily available. To that end, a hydraulic motor-driven cutting module that aims to combine cutting and drug delivery is presented. The hydraulic motor prototype developed has an outside diameter (OD) of ~4 mm (twice the target size) and a 1 mm drive shaft to attach a cutter. Four different designs were explored and fabricated using additive manufacturing. The benchtop experimental data of the prototypes are presented herein. For the prototype motor with fluid inlet perpendicular to the blades, the average angular velocity was 10,593 RPM at a flowrate of 3.6 mL/s and 42,597 RPM at 10.1 mL/s. This design was numerically modeled using 3D-transient simulations in ANSYS CFX (version 2022 R2) to determine the performance characteristics and the internal resistance of the motor. Simplified mathematical models were also used to compute and compare the peak torque with the simulation estimates. The viability of current design represents a crucial milestone in scaling the hydraulic motor to a 2 mm OD to power a microcutter.

Routine chest radiography after thoracostomy tube removal and during postoperative follow-up is not necessary after lung resection.

OBJECTIVES: The need for routine chest radiography following chest tube removal after elective pulmonary resection may be unnecessary in most patients. The purpose of this study was to determine the safety of eliminating routine chest radiography in these patients. METHODS: Patients who underwent elective pulmonary resection, excluding pneumonectomy, for benign or malignant indications between 2007 and 2013 were reviewed. Patients with in-hospital mortality or without routine follow-up were excluded. During this interval, our practice transitioned from ordering routine chest radiography after chest tube removal and at the first postoperative clinic visit to obtaining imaging based on symptomatology. The primary outcome was changes in management from results of chest radiography obtained routinely versus for symptoms. Characteristics and outcomes were compared using the Student t test and chi-square analyses. RESULTS: A total of 322 patients met inclusion criteria. Ninety-three patients underwent a routine same-day post-pull chest radiography, and 229 patients did not. Thirty-three patients (14.4%) in the nonroutine chest radiography cohort received imaging for symptoms, in whom 8 (24.2%) resulted in management changes. Only 3.2% of routine post-pull chest radiography resulted in management changes versus 3.5% of unplanned chest radiography with no adverse outcomes (P = .905). At outpatient postoperative follow-up, 146 patients received routine chest radiography; none resulted in a change in management. Of the 176 patients who did not have planned chest radiography at follow-up, 12 (6.8%) underwent chest radiography for symptoms. Two of these patients required readmission and chest tube reinsertion. CONCLUSIONS: Reserving imaging for patients with symptoms after chest tube removal and follow-up after elective lung resections resulted in a higher percentage of meaningful changes in clinical management.

Impact of Environmental Exposures on Lung Cancer in Patients Who Never Smoked.

BACKGROUND: Despite the rising incidence of lung cancer in patients who never smoked, environmental risk factors such as ambient air pollution in this group are poorly described. Our objective was to identify the relationship of environmental exposures with lung cancer in patients who never smoked. METHODS: A prospectively collected database was reviewed for all patients with non-small cell lung carcinoma (NSCLC) who underwent resection from 2006 to 2021. Environmental exposures were estimated using the geocoded home address of patients. Logistic regression was used to determine the association of clinical and environmental variables with smoking status. Kaplan-Meier and Cox proportional hazards analyses were used to assess survival. RESULTS: A total of 665 patients underwent resection for NSCLC, of which 67 (10.1%) were patients who never smoked and 598 (89.9%) were current/former smokers. Patients who never smoked were more likely of white race (p = 0.001) and had well-differentiated tumors with carcinoid or adenocarcinoma histology (p < 0.001). Environmental exposures were similar between groups, but patients who never smoked had less community material deprivation (p = 0.002) measured by household income, education, health insurance, and vacancies. They had improved overall survival (p = 0.012) but equivalent cancer recurrence (p = 0.818) as those who smoked. In univariable Cox analyses, fine particulate matter (HR: 1.447 [95% CI 1.197-1.750], p < 0.001), distance to nearest major roadway (HR: 1.067 [1.024-1.111], p = 0.002), and greenspace (HR: 0.253 [0.087-0.737], p = 0.012) were associated with overall survival in patients who never smoked. CONCLUSIONS: Lung cancer patients who never smoked have unique clinical and pathologic characteristics, including higher socioeconomic status. Interventions to reduce environmental exposures may improve lung cancer survival in this population.

Design and Modeling of a Miniature Hydraulic Motor for Powering a Cutting Tool for Minimally Invasive Procedures.

Miniaturization of multifunctional instruments is key to evolving less invasive medical procedures. The current work outlines steps towards developing a miniature motor to power a cutting tool of a millimeter-scale robot/device (target outside diameter ~2 mm) for minimally invasive procedures. Multiple motor concepts were explored and ranked using a Pugh matrix. The single-rotor hydraulic design was deemed most viable for prototyping and scale-down to the target size. Prototypes were manufactured to be progressively smaller using additive manufacturing. The smallest prototype fabricated was 2:1 scale of the desired final size with a 2 mm outside diameter (OD) rotor and a device OD of 4 mm. The scaled prototypes with an 8 mm rotor were lab tested and achieved average speeds of 5000-6000 RPM at a flowrate of 15-18 mL/s and 45 PSI water pressure. Ansys CFX was used as a design tool to explore the parameter space and 3D transient simulations were implemented using the immersed solid method. The predicted rotor RPM from the modeling matched the experimental values within 3% error. The model was then used to develop performance curves for the miniature hydraulic motor. In summary, the single-rotor hydraulic design shows promise for miniaturization to the target 2 mm size.

A decade of surgical outcomes in a structured lung cancer screening program.

OBJECTIVE: Lung cancer screening can decrease mortality. The majority of screen-detected cancers are early stage and undergo surgical resection. However, there are little data regarding the outcomes of surgical treatment outside of clinical trials. The purpose of this study was to compare the outcomes of curative resection for screen-detected lung cancers with nonscreened, incidentally detected cancers at an institution with a structured screening program. METHODS: Patients undergoing lung cancer curative resection from January 2012 to June 2021 were identified from a prospective database. Baseline patient characteristics, tumor characteristics, and outcomes were compared between cancer detected from screening and cancer detected incidentally. RESULTS: There were 199 patients in the incidental group and 82 patients in the screened group. Mean follow-up was 33.3 ± 25 months. The screened group had more African Americans (P = .04), a higher incidence of emphysema (P = .02), less prior cancers (P < .01), and more pack-years smoked (P < .01). The screened group had a smaller size (1.74 vs 2.31 cm, P < .01); however, pathologic stage was similar, with the majority being stage I. Postoperative morbidity, 30-day mortality, and overall and recurrence-free survival were similar between groups. Only 48.7% of the incidental group met current US Preventative Services Task Force screening criteria (age 50-80 years, ≥20 pack-year smoking history). CONCLUSIONS: Screen-detected lung cancers have excellent postoperative and long-term outcomes with curative resection, similar to incidentally detected cancers. A large portion of incidentally detected lung cancers do not meet current screening guidelines, which is an opportunity for further refinement of eligibility.

Lung cancer screening utilization rate varies based on patient, provider, and hospital factors.

OBJECTIVE: Low-dose computed tomography has been proven to reduce mortality, yet utilization remains low. The purpose of this study is to identify factors that impact the utilization of lung cancer screening. METHODS: We performed a retrospective review of our institution's primary care network from November 2012 to June 2022 to identify patients who were eligible for lung cancer screening. Eligible patients were 55 to 80 years of age and current or former smokers with at least a 30 pack-year history. Analyses were performed on the screened populations and patients who met eligibility criteria but were not screened. RESULTS: A total of 35,279 patients in our primary care network were current/former smokers aged 55 to 80 years. A total of 6731 patients (19%) had a 30 pack-year or more cigarette history, and 11,602 patients (33%) had an unknown pack-year history. A total of 1218 patients received low-dose computed tomography. The utilization rate of low-dose computed tomography was 18%. The utilization rate was significantly lower (9%) if patients with unknown pack-year history were included (P < .001). The utilization rates between primary care clinic locations were significantly different (range, 18% vs 41%, P < .05). Utilization of low-dose computed tomography on multivariate analysis was associated with Black race, former smoker, chronic obstructive pulmonary disease, bronchitis, family history of lung cancer, and number of primary care visits (all P < .05). CONCLUSIONS: Lung cancer screening utilization rates are low and vary significantly on the basis of patient comorbidities, family history of lung cancer, primary care clinic location, and accurate documentation of pack-year cigarette history. The development of programs to address patient, provider, and hospital-level factors is needed to ensure appropriate lung cancer screening.

Cardiac Surgery Exposure in General Surgery Residency-A Survey of General Surgery Residency Program Directors.

BACKGROUND: Little is known regarding how much exposure general surgery residents have to cardiac surgery, despite cardiothoracic (CT) surgery being an offered postresidency fellowship and career. Exposure to a subspecialty is important in shaping residents' interests and career decisions. METHODS: A survey was sent to all general surgery program directors via the Association of Program Directors in Surgery examining cardiac surgery exposure during training. The survey examined the presence of operative rotations in cardiac surgery and cardiac critical care, portions of cases residents were permitted to perform, cardiac surgery mentorship and education, and perceived biases in applying to cardiac surgery. Differences between programs with and without cardiothoracic training programs were analyzed. RESULTS: In total, 44% (102/230) of program directors responded to the survey. Residents were involved in operative cardiac and cardiac ICU rotations in 61 programs (69.8%) and 39 programs (38.2%), respectively. Twenty programs (19.6%) had a dedicated cardiothoracic surgery training program and these programs had significantly more graduates who aspired to be cardiac surgeons (M = 2.75, SD = 2.47) compared to hospitals with no CT programs (M = 1.43, SD = 1.41; p = 0.031). 35.3% of program directors reported resident concern over family life. CONCLUSIONS: There is a notable heterogeneity in general surgery resident exposure to cardiac surgery, cardiac ICU, and cardiac surgery mentorship. Increased exposure, mentorship and mitigating resident concern over the impact of social factors on cardiac surgical careers should be key areas of focus to ensure continued encouragement of future trainees and surgeons.

Improving Lung Cancer Diagnosis with CT Radiomics and Serum Histoplasmosis Testing.

BACKGROUND: Indeterminate pulmonary nodules (IPN) are a diagnostic challenge in regions where pulmonary fungal disease and smoking prevalence are high. We aimed to determine the impact of a combined fungal and imaging biomarker approach compared with a validated prediction model (Mayo) to rule out benign disease and diagnose lung cancer. METHODS: Adults ages 40 to 90 years with 6-30 mm IPNs were included from four sites. Serum samples were tested for histoplasmosis IgG and IgM antibodies by enzyme immunoassay and a CT-based risk score was estimated from a validated radiomic model. Multivariable logistic regression models including Mayo score, radiomics score, and IgG and IgM histoplasmosis antibody levels were estimated. The areas under the ROC curves (AUC) of the models were compared among themselves and to Mayo. Bias-corrected clinical net reclassification index (cNRI) was estimated to assess clinical reclassification using a combined biomarker model. RESULTS: We included 327 patients; 157 from histoplasmosis-endemic regions. The combined biomarker model including radiomics, histoplasmosis serology, and Mayo score demonstrated improved diagnostic accuracy when endemic histoplasmosis was accounted for [AUC, 0.84; 95% confidence interval (CI), 0.79-0.88; P < 0.0001 compared with 0.73; 95% CI, 0.67-0.78 for Mayo]. The combined model demonstrated improved reclassification with cNRI of 0.18 among malignant nodules. CONCLUSIONS: Fungal and imaging biomarkers may improve diagnostic accuracy and meaningfully reclassify IPNs. The endemic prevalence of histoplasmosis and cancer impact model performance when using disease related biomarkers. IMPACT: Integrating a combined biomarker approach into the diagnostic algorithm of IPNs could decrease time to diagnosis.

The Impact of Enhanced Recovery After Surgery on Persistent Opioid Use Following Pulmonary Resection.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been associated with improved perioperative outcomes after thoracic surgery; however, the impact on long-term opioid use remains unknown. The aim of our study was to evaluate the effects of ERAS on long-term opioid use. METHODS: Patients who underwent pulmonary resection were identified from a prospectively maintained database and linked to the regional prescription drug monitoring program. Outcomes were compared between pre-ERAS (February 2016 to November 2018) and ERAS (December 2018 to June 2020) cohorts. Our ERAS protocol included regional anesthetic, multimodal pain control, and protocolized rehabilitation. RESULTS: We analyzed 240 pulmonary resections, 64.6% (n = 155) in the pre-ERAS era and 35.4% (n = 85) in the ERAS era. Baseline characteristics were similar; however, more patients in the ERAS cohort underwent minimally invasive surgery (67.7% vs 87.9%; P = .002). Median length of stay was reduced (5 days vs 4 days; P = .03) upon implementation of ERAS, with no change in perioperative complications or readmission rate. On multivariate analysis, ERAS was associated with decreased total inpatient morphine milligram equivalent and discharge morphine milligram equivalent. However, both long-term opioid use up to 1 year postoperatively and new persistent opioid use remained similar despite implementation of ERAS. On multivariate analysis, implementation of ERAS was not associated with a reduction in opioid use 14 to 90 days postoperatively or persistent opioid use 90 to 180 days postoperatively. CONCLUSIONS: Despite short-term opioid reduction, long-term opioid use persisted after implementation of ERAS. Additional strategies to monitor for and avoid opioid dependence are urgently needed to prevent chronic opioid use after pulmonary resection.

Does Molecular Profiling of KRAS-Mutant Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Help in Treatment Strategy Planning?

Background: Several studies suggest that patients with KRAS-mutant NSCLC fail to benefit from standard systemic therapies and do not respond to EGFR inhibitors. Most recently, KRAS 12c data suggest specific treatment for improving ORR and OS. There is a clear need for therapies specifically developed for these patients. Moreover, data that might be suggestive of a response to specific therapies, such as BRCA1, are needed, and two mutations that were studied in other malignancies show more response to PARP inhibitors. Molecular profiling has the potential to identify other potential targets that may provide better treatment and novel targeted therapy for KRAS-mutated NSCLC. Methods: We purified RNA from archived tissues of patients with stage I and II NSCLC with wild-type (wt) and mutant (mt) KRAS tumors; paired normal tissue adjacent to the tumor from 20 and 17 patients, respectively, and assessed, using real-time reverse transcriptase−polymerase chain reaction (RT-PCR), the expression of four genes involved in DNA synthesis and repair, including thymidylate synthase (TS), BRCA1, ECCR1, RAP80, and the proto-oncogene SRC. Additionally, we assessed the expression of PD-L1 in mt KRAS tumors with immunohistochemistry using an antibody against PD-L1. Results: Our results show that in mtKRAS tumors, the level of expression of ERCC1, TS, and SRC was significantly increased in comparison to paired normal lung tissue (p ≤ 0.04). The expression of BRCA1 and RAP80 was similar in both mt KRAS tumors and paired normal tissue. Furthermore, the expression of BRCA1, TS, and SRC was significantly increased in wt KRAS tumors relative to their expression in the normal lung tissue (p < 0.044). The expression of ERCC1 and RAP80 was similar in wt KRAS tumors and paired normal tissue. Interestingly, SRC expression in mtKRAS tumors was decreased in comparison to wt KRAS tumors. Notably, there was an expression of PD-L1 in the tumor and stromal cells in a few (5 out of 20) mtKRAS tumors. Our results suggest that a greater ERCC1 expression in mt KRAS tumors might increase platinum resistance in this group of patients, whereas the greater expression of BRCA1 in wt KRAS tumor might be suggestive of the sensitivity of taxanes. Our data also suggest that the combination of an SRC inhibitor with a TS inhibitor, such as pemetrexed, might improve the outcome of patients with NSCLC and in particular, patients with wt KRAS tumors. PD-L1 expression in tumors, and especially stromal cells, suggests a better outcome. Conclusion: mt KRAS NSCLC patients might benefit from a treatment strategy that targets KRAS in combination with therapeutic agents based on pharmacogenomic markers, such as SRC and BRCA1. mtKRAS tumors are likely to be platinum-, taxane-, and pemetrexed-resistant, as well as having a low level of PD-L1 expression; thus, they are less likely to receive single-agent immunotherapy, such as pembrolizumab, as the first-line therapy. wt KRAS tumors with BRCA1 positivity tend to be sensitive to taxane therapy and, potentially, platinum. Our results suggest the need to develop targeted therapies for KRAS-mutant NSCLC or combine the targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor.

Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer.

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC.

A Structured Program Maximizes Benefit of Lung Cancer Screening in an Area of Endemic Histoplasmosis.

BACKGROUND: Lung cancer screening with low-dose computed tomography has demonstrated at least a 20% decrease in lung cancer-specific mortality, but it has the potential harm of unnecessary invasive procedures performed because of false-positive results. This study reports the outcomes of a structured multidisciplinary lung cancer screening program in an area of endemic histoplasmosis. METHODS: A retrospective review of patients undergoing lung cancer screening from December 2012 to March 2019 was conducted. Findings suggestive of lung cancer were presented to a multidisciplinary thoracic tumor board. Patients were assigned to interval imaging follow-up, additional diagnostic imaging, or referral for an invasive procedure. Invasive procedures were then compared between benign and malignant diseases. RESULTS: A total of 4087 scans were performed on 2129 patients; 372 (9.1%) were suspicious and were presented to a multidisciplinary thoracic tumor board. Ultimately, 108 procedures were performed: 55 bronchoscopies, 7 percutaneous biopsies, and 46 operations. A total of 25 patients (1.2%) underwent bronchoscopy resulting in benign pathologic findings, significantly associated with an indication of an endobronchial lesion (P = .01). All percutaneous biopsy specimens revealed malignancy. Five patients (0.2%) who underwent resection had benign disease. Lung cancer was diagnosed in 67 patients (3.1% of the entire cohort), 46 of whom had stage I or II disease. CONCLUSIONS: Lung cancer screening in a structured, multidisciplinary program successfully identifies patients with early-stage lung cancer with limited unnecessary surgical interventions. Patients with isolated endobronchial lesions should undergo short interval imaging follow-up to avoid bronchoscopy for benign disease. Future studies to minimize unnecessary procedures could incorporate biomarkers and advanced imaging analysis into risk assessment models.

Impact of Integrated Thoracic Residency on General Surgery Residents' Thoracic Operative Volume.

BACKGROUND: Integrated thoracic surgery (I-6) programs have become popular over traditional general surgery (GS) pathways since their inception in 2007. However the effect of I-6 programs on GS resident training remains unknown. The purpose of this study was to evaluate the effect of I-6 programs on the thoracic operative experience of co-located GS residents. METHODS: Thoracic surgery cases recorded by residents in GS programs co-located with I-6 programs until 2019 were analyzed. Cases were reviewed 5 years before (TSR-5) through 5 years after (TSR-5) the matriculation of the first thoracic resident in the co-located I-6 program. To contextualize the overall trends in the field Accreditation Council for Graduate Medical Education GS resident case logs from 1990 to 2018 were analyzed and total thoracic surgery cases recorded. Statistical analysis was performed with linear regression. RESULTS: Residents in 19 GS programs with co-located I-6 programs showed an increase in total thoracic cases from 3710 to 4451 (Δ/year of +85.05 cases a year; P = .03) balanced by an increase in GS residents from 107 to 126 (Δ/year of +1.45; P = .01) with no significant overall change in the median thoracic operative case volume (31.00 at both thoracic residency before and after 5 years). Nationally from 1990 to 2018 there was no change in the total thoracic operative experience for GS graduates. CONCLUSIONS: The introduction of I-6 programs did not negatively impact thoracic operative experience for residents in co-located GS programs. Adequate training of both I-6 and GS residents at the same institution is feasible.

Offering lung resection to current smokers: An opportunity for more equitable care.

OBJECTIVE: Minority patients with lung cancer are less likely to undergo surgical resection and experience worse survival than non-Hispanic White patients. Currently, 40% of thoracic surgeons require smoking cessation before surgery, which may disproportionately affect minority patients. Our objective was to assess the risk of smoking status on postoperative morbidity and mortality among patients with lung cancer. METHODS: A prospectively maintained institutional database was queried for all patients who underwent surgical resection of a primary lung malignancy between 2006 and 2020. Operative mortality, major morbidity, and a composite of morbidity and mortality were compared between current smokers and prior smokers. RESULTS: A total of 601 patients underwent resection, and 236 (39.3%) were current smokers. Current smokers were more likely to be younger (P < .01), to have a greater pack-years history (P = .03), and to have worse pulmonary function test results (P < .01). Pretreatment stage, surgical approach, and extent of resection were similar between groups. There was no difference in operative mortality (0.9% vs 1.9%, P = .49), major morbidity (12.7% vs 9.3%, P = .19), or composite major morbidity and mortality between groups (13.1% vs 9.3%, P = .14). After adjusting for pulmonary function status, current smoking status was not associated with mortality or major morbidity on multivariable logistic regression (odds ratio, 1.51; 95% confidence interval, 0.76-3.03, P = .24). CONCLUSIONS: Current smokers experienced similar rates of mortality and major morbidity as prior smokers. In the context of continued racial and ethnic disparities in lung cancer survival, in particular decreased resection rates among minorities, smoking cessation requirements should not delay or prevent operative intervention for lung cancer.