Meta-Analysis of Rates and Risk Factors for Local Recurrence in Surgically Resected Patients With NSCLC and Differences Between Asian and Non-Asian Populations.

Introduction: Postoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People's Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.3% and 28.1% (46% of which were mediastinal recurrences), respectively. We performed a meta-analysis of patients with pathologic (p) N0 to N2 disease to evaluate the risk factors for LR and to explore possible differences in recurrence risk between Asian population (AP) and non-Asian population (NAP). Methods: We identified all original studies of curative NSCLC surgical resection which reported risk of LR between January 1, 2000, and January 10, 2021, excluding studies with less than 10 LR, patients with metastatic disease, or any neoadjuvant therapy. A total of 87 studies were identified with pN0 to N2 disease; of these, 56 were of high quality (HQ) on the basis of the Newcastle-Ottawa Scale. For each risk factor, we derived pooled relative risk (RR) and 5-year rate estimates using random-effects models. Results: Overall, the three significant highest pooled RRs (95% confidence intervals) for LR were pN2 versus pN0 (3.01, 1.39-6.55), lymphovascular invasion (1.92, 1.58-2.33), and advanced pT3-4 stage versus pT1 (1.86, 1.53-2.25). For HQ studies, the highest RRs for LR were lymphovascular invasion (1.94, 1.57-2.40), sublobar versus lobar resection (1.86, 1.46-2.36), and pN1 versus pN0 (1.84, 1.37-2.47), but pN2 versus pN0 was no longer significant (3.0, 0.57-15.61), on the basis of only two eligible studies. The RRs for LR were consistent for most factors in AP and NAP, although the RR for male versus female sex was higher in AP (1.44, 1.21-1.72) than in NAP (1.09, 0.99-1.19). Where reported, the pooled rate of LR at 5 years was lower in AP (12.0%) than in NAP (22.7%), despite similar overall 5-year recurrence rates (both LR and distal) in both populations: 38.0% in AP and 37.3% in NAP. Nevertheless, a lower 5-year mortality rate was noted in AP (24.3%) than in NAP (45.9%). Conclusions: There is little high-quality evidence to support the hypothesis that pN2 disease is a risk factor for LR, but LR seems to be lower in Asians. Prospective evaluation of LR factors and rates may be necessary before further prospective evaluation of PORT, because it may not depend on nodal status alone. Recurrence rates may differ in Asians. The impact of mutational status and modern treatment including targeted therapies and immune checkpoint inhibitors is inadequately studied.

Ex vivo pneumostasis evaluation of a variable-height staple design.

OBJECTIVE: This study examined the effect of using a variable-height staple construct containing three rows of staples with heights of 3.0, 3.5, and 4.0 mm (staple leg length, medial to lateral) versus standard three-row single-height staplers (with staple heights of either 3.5 or 4.8 mm) for pneumostasis in healthy porcine and canine lung parenchyma to determine whether a single stapler that uses variable staple heights could perform as well as, or better than, existing single-height stapling devices. The work presented here used healthy animal tissues, in lieu of diseased tissue, which is extremely difficult to obtain and quantify. METHODS: Briefly, fresh explanted porcine and canine trachea-lung blocs were used for all testing. Tissue thicknesses were measured with a custom-design spring-loaded caliper before stapling with control and test articles to ensure that the tissue was of "appropriate" thickness for the stapler size (staple height) selected (per manufacturer's instructions for use). All tissue measurements were comparable across each area of lung tested, and both test and control devices were fired into the same tissue thicknesses. After stapling, the lungs were submerged in water, insufflated, checked for air leaks at four discrete (increasing) pressures, and scored using a predetermined scale. Statistical analysis was performed for n = 26 (3.5-mm staples), n = 29 (4.8-mm staples), and n = 26 or 29 (paired to the standard group) for the variable-height stapler (3.0-, 3.5-, and 4.0-mm staples). RESULTS: The results demonstrated that the test article comprising three rows of variable-height staples provided comparable pneumostasis with the standard three-row single-height staplers (with staple heights of either 3.5 or 4.8 mm) under the test conditions described. CONCLUSIONS: A novel test article containing three rows of staples with heights of 3.0, 3.5, and 4.0 mm (variable-height stapler) showed promising results when compared with standard commercially available single-height staplers, performing as well as or better than the standard single-height staplers. This work demonstrates important first steps to proving equivalent device performance, which might facilitate the use of a variable-height stapler in place of multiple single-height staplers.

Comparison of endostapler performance in challenging tissue applications.

BACKGROUND: Surgical staplers are frequently used in a variety of applications, demanding exacting instrument performance over a huge range of tissue compositions and disease states. The shape of a staple that is formed by a stapling device is one industry-accepted indicator of device performance; typically a B-shaped staple is considered the gold standard for staple formation. This B shape allows blood flow through the tissue, which is one important factor in the healing events that take place clinically after stapling. With the use of an animal model, this ex vivo study investigated staple formation when thick tissue endoscopic staplers were used on challenging and variable tissue. The setting was a corporate institution in the United States. METHODS: Two 60-mm linear endoscopic thick tissue reloads, a varied-height stapler (VHS), and a single-height stapler (SHS) were fired on 7 different regions of porcine stomach. Resultant staple formation was assessed per region of the stomach and evaluated for proper B-shaped staple formation and staple malformation. RESULTS: The VHS reload had significantly better B-shaped formation (P<.001) for all regions of the stomach and reduced occurrence of malformed staples in 5 of the 7 regions compared with the SHS reload, wherein the remaining 2 regions exhibited comparable malform occurrence. CONCLUSIONS: This study compared 2 thick tissue reloads and found that the VHS reload had superior outcomes, with respect to staple formation, compared with the SHS reload.

New rod-plate anterior instrumentation for thoracolumbar/lumbar scoliosis: biomechanical evaluation compared with dual-rod and single-rod with structural interbody support.

STUDY DESIGN: A new rod-plate anterior implant was designed to provide plate fixation at the cephalad and caudal-end segments of a 5-level anterior spine construct. Biomechanical testing was performed on calf spines instrumented with 5-segment anterior scoliosis constructs. OBJECTIVES.: To analyze the initial and post-fatigue biomechanical performance of the new implant, and compare it to an anterior dual-rod construct and a single-rod construct with interbody cages. SUMMARY OF BACKGROUND DATA: Using single-rod anterior instrumentation for thoracolumbar and lumbar scoliosis, an unacceptable incidence of loss of correction, segmental kyphosis, and pseudarthrosis has been reported. Inadequate construct stiffness due to early postoperative bone-screw interface failure, especially at cephalad and caudal-end vertebrae, has been implicated as the cause of these complications. METHODS: Thirty calf spines were instrumented over 5 segments with: (1) single-rod augmented with rod-plate implants, (2) dual-rod construct, and (3) single-rod with titanium mesh cages. Stiffness in flexion-extension and lateral bending modes was determined initially and post-cyclical loading by measuring segmental range of motion (ROM). Post-fatigue screw pullout tests were also performed. RESULTS: In lateral bending, the caudal-end segmental ROM for rod-plate construct was 54% less than single-rod with cages construct (P < 0.05), with no difference between rod-plate and dual-rod constructs. In flexion-extension, the rod-plate construct showed 45% to 91% (initial test) and 84% to 90% (post-fatigue) less ROM than the single-rod with cages construct (P < 0.001). Again, there was no difference between rod-plate and dual-rod constructs at the cephalad and caudal-end segments. Post-fatigue screw pullout strengths of the rod-plate construct were significantly greater than those of the dual-rod and single-rod with cages constructs (P < 0.05). CONCLUSIONS: The rod-plate construct was significantly stiffer and provided greater stability of bone-screw interface than the single-rod with cages construct. It achieved similar stiffness and improved bone-screw interface stability compared to dual-rod construct.

Analysis of fixation methods for vertical shear fractures of the medial malleolus.

OBJECTIVE: To evaluate 4 different fixation methods used to treat vertical shear fractures of the medial malleolus. METHODS: Eighty polyurethane models of the distal tibia were osteotomized in a reproducible manner to create a vertical shear fracture of the medial malleolus. Twenty specimens were then randomly assigned to 1 of 4 fixation groups. Two fixation groups used a neutralization plate, whereas 2 groups were screw-only constructs. Ten of the specimens in each group were then randomly assigned to undergo either offset axial or offset transverse loading. RESULTS: The construct using a neutralization plate with 2 screws in the distal fragment exhibited greater stiffness in offset axial loading compared with the screw-only constructs placed an equivalent distance from the tibial plafond. All specimens in the group with the properly applied neutralization plate exhibited elastic deformation, whereas the majority of the specimens in all other groups showed residual displacement or catastrophic failure of the construct. CONCLUSION: Fixation of vertical shear fractures of the medial malleolus with a properly applied neutralization plate offers a significant mechanical advantage over screw-only constructs.

Mechanical effect of posterior wire or half-pin configuration on stabilization utilizing a model of circular external fixation of the foot.

BACKGROUND: Numerous studies have addressed biomechanical characteristics of circular external fixation of long bones. The objective of the present study was to evaluate stabilization of a simulated foot model using external fixation with either calcaneal tensioned stopper wires or half-pins. METHODS: Fixation configurations of the calcaneus included two parallel wires, two wires crossing at either 30 degrees or 45 degrees, a 4-mm- and 5-mm-diameter single half-pin, or two half-pins inserted at a cross-angle of either 45 degrees or 90 degrees. All frames were tested in axial compression, anteroposterior (AP) bending, and mediolateral (ML) bending. RESULTS: An increase in wire cross-angle improved the axial and AP bending stabilization but had no influence on ML bending. Utilization of a single calcaneal half-pin instead of two cross-wires resulted in a considerable reduction in ML bending stabilization. Frame configurations with two half-pins substantially improved axial and ML bending stabilization. Due to the medial location of the metatarsal wire stopper, an increase in half-pin cross-angle significantly improved ML bending stiffness under lateral foot loading. Under the medial foot loading, however, the half-pin cross-angle had no effect on ML bending stabilization. Replacement of cross-wires with two half-pins significantly improved the AP bending stiffness only when the half-pin cross-angle was reduced to 45 degrees. In all modes of two half-pin frame loading, the half-pin diameter had a substantial effect on foot stabilization. CONCLUSIONS: Although the wire cross-angle, half-pin cross-angle, and half-pin diameter affect the stability of foot circular external fixation, the influence of these mechanical parameters on foot stabilization is dependent on the mode and location of loading. CLINICAL RELEVANCE: The results of the present mechanical testing can be utilized as a useful guideline for the optimization of circular external fixation of the foot.

A mechanical comparison of veterinary linear external fixation systems.

OBJECTIVE: To compare the fixation rigidity of recently developed external fixation systems (EFSs) to that of the traditional Kirschner-Ehmer (KE) system. STUDY DESIGN: In vitro biomechanical study. SAMPLE POPULATION: Five different EFSs (KE, Secur-U, small SK carbon fiber, small SK titanium, large SK carbon fiber) were assembled into 7 frame geometries to stabilize Delrin plastic rods with a 1-cm gap. METHODS: External skeletal fixation (ESF) constructs were tested in axial compression, torsion, medial-lateral bending, and cranial-caudal bending. Testing was conducted within the elastic range of each fixator. Mean stiffness in each mode was determined from the slope of the linear portion of the load-deformation curve. Comparison of stiffness values of each EFS within each loading mode and frame type was performed with 1-way analysis of variance (P <.05). RESULTS: Mean stiffness values were significantly higher for the large SK EFS in all frame types compared with KE but were equal in torsional stiffness in the double-bar type 1a frame. The small SK EFS with titanium connecting bar had greater stiffness than the KE in all modes for frame types Ia, Ia-accessory bar, and II-modified. No overall difference was detected between the KE EFS and the small SK with carbon fiber rod. The stiffness of the Secur-U type Ia frame with augmentation plate was significantly greater than the KE type Ia with accessory bar. CONCLUSIONS: The newer external fixation systems evaluated in this study provided fixation rigidity equal to or greater than that of the KE system. CLINICAL RELEVANCE: EFSs with increased frame rigidity should permit the use of less complex frame designs while providing fracture stability.

Experimental tibial plateau fractures augmented with calcium phosphate cement or autologous bone graft.

BACKGROUND: Depression fractures of the tibial plateau are often managed with use of internal fixation and autologous bone-grafting to maintain an anatomical reduction. Bone-grafting, however, provides only limited stability. As calcium phosphate cements have appropriate mechanical properties, they may provide a more suitable alternative. The objective of this study was to compare the effect of a calcium phosphate cement with that of impacted cancellous autograft for maintaining an anatomical reduction in an experimental model of a tibial plateau fracture. METHODS: Standardized cylindrical subchondral defects that were 8 mm in diameter and 10 mm deep were created bilaterally beneath the subchondral bone of the articular cartilage in the lateral tibial plateau of goats. An osteotome was used to fracture the overlying subchondral plate and articular cartilage. The plateau fracture fragment was completely depressed into the subchondral defect and then was anatomically reduced. The defects were randomly filled with either calcium phosphate cement or cancellous autograft. No internal fixation was used. The tibiae were harvested at varying time-periods that ranged from twenty-four hours to eighteen months. The stiffness of the healing augmented plateau fractures was determined. Histological specimens were assigned a score for degenerative changes. Loss of anatomic reduction was demonstrated in photomicrographs, and the amount of subsidence of the osteochondral fragment was measured in whole-mount histological sections. RESULTS: The prevalence and degree of fracture subsidence was significantly reduced at all time-points in the defects treated with calcium phosphate cement compared with those filled with autograft (p < 0.05). There were no significant differences in fracture stiffness between the two treatment groups at any of the time-points examined. The calcium phosphate cement was rapidly resorbed, and the volume fraction of the calcium phosphate cement was decreased to 4% at six months. The trabecular bone volume in the defects was restored to that of the intact controls at six months in both treatment groups. CONCLUSIONS: Cancellous autograft did not maintain an anatomical reduction of the tibial plateau fractures in this model. In contrast, augmentation with calcium phosphate cement prevented subsidence of the fracture fragment and maintained articular congruency as the fracture healed. The improved articular congruency reduced the prevalence and severity of degenerative changes in the joint.

Subchondral defects in caprine femora augmented with in situ setting hydroxyapatite cement, polymethylmethacrylate, or autogenous bone graft: biomechanical and histomorphological analysis after two-years.

Juxta-articular defects pose significant challenges due to the high risk of fracture of the subchondral plate and articular cartilage. We evaluated the mechanical and histomorphological repair process of caprine subchondral femoral defects augmented with either a bioresorbable in situ setting hydroxyapatite cement (HAC), polymethylmethacrylate (PMMA), autogenous bone graft (AG), or left empty. Twelve-mm subchondral defects were made bilaterally in the medial femoral condyles of skeletally mature goats and augmented with a test material or left empty. Femurs were harvested at varying time periods out to 2 years and evaluated for subchondral stiffness and histomorphological indices. Several defects augmented using autograft or left empty sustained focal fracture of the subchondral plate. No HAC or PMMA augmented defects showed evidence of subchondral fracture. The HAC and PMMA augmented defects showed comparable stiffness at all time points. The mean volume fraction of HAC remaining within the defects progressively decreased from 96% at 24 h to 38% at 2 years. The new bone replacing the HAC appeared to have normal physiological architecture and orientation. In situ setting hydroxyapatite cement may be a viable alternative for the repair of subchondral defects with an important advantage that while undergoing gradual resorption and replacement with host bone, mechanical integrity of the skeletal defect is maintained.

Thoracoscopic discectomy and fusion in an animal model: safe and effective when segmental blood vessels are spared.

STUDY DESIGN: Disc-endplate excision and spine fusion were compared in animals randomly assigned to segmental vessel-spared and segmental vessel-ligated groups in an in vivo goat model of anterior spine discectomy and fusion using thoracoscopic techniques. OBJECTIVES: To compare safety and completeness of disc and endplate excision, and to perform a histologic and biomechanical comparison between fusion masses when the segmental vessels are spared and when they are ligated using thoracoscopic techniques. SUMMARY OFF BACKGROUND DATA: Because thoracoscopy is relatively new and technically demanding, many surgeons ligate the segmental blood vessels to enhance spine exposure and limit the risk of injury during discectomy and fusion. Although rare, spinal cord compromise secondary to segmental vessel ligation has been reported. METHODS: This study was divided into two phases. In Phase 1, 10 mature goats were randomly assigned to either the segmental vessel-ligated or the segmental vessel-spared group. Disc and endplate excision was performed at six consecutive thoracic levels in each animal (30 levels per group). The animals were killed, and the depth of disc excision was measured in the transverse and sagittal planes. The vertebral bodies then were separated through the disc space; photographic images of the endplates were digitized, and the area of endplate excision was calculated. In Phase 2, 12 mature goats were randomly assigned to the segmental vessel-ligated or vessel-spared group, and five noncontiguous thoracic segments were fused using autologous iliac crest graft. At 4 months the animals were killed, and the spines were harvested. At each disc level, the three-dimensional rotational and translational motions were analyzed and histomorphometric analysis was performed. RESULTS: Phase 1: Each animal survived the operative procedure, and no surgical complications occurred. No difference was found between vessel-ligated and vessel-spared groups in operative time (21.8 vs 22.7 minutes per disc), blood loss (97 vs 159 mL), or transverse (81% vs 74%) or sagittal (85% vs 85%) disc excision. The total area of endplate excision was 70% in the vessel-ligated group and 67% in the vessel-spared group (P > 0.1). Phase 2: Biomechanical testing demonstrated no difference in stiffness of the fused segments between the two groups in flexion-extension or axial rotation. However, greater flexibility in lateral bending was found in the specimens whose vessels were ligated (P < 0.05). The percentage of trabecular bone volume was similar between the two groups. CONCLUSIONS: The segmental vessels in the thoracic spine can be effectively spared without injury during disc excision and fusion. Although slightly more disc area was excised with ligation of the vessels, this was not statistically significant, and the fusion mass was similar between the two groups. Sparing the segmental vessels may provide blood supply that aids fusion mass, and the result may be greater spine stiffness in the coronal plane. Sparing the segmental vessels during thoracoscopic anterior disc excision and fusion can be safe. It should be considered in patients with a high risk for neurologic injury because of decreased spinal cord perfusion in revision surgery, severe kyphosis, congenital anomalies. Because the neurologic risk of vessel ligation has not been clearly established for idiopathic scoliosis, the surgeon will have to consider the risk-benefit ratio of adopting these methods when deciding not to ligate vessels in these patients.

Stabilization of a short juxta-articular bone segment with a circular external fixator.

The objective of the current study was to evaluate the stabilization of a simulated juxta-articular bone segment with a circular external fixator, and to determine which method of fixation improved bending stabilization while preserving the axial dynamization of a three-wire configuration. Frames were divided into three groups: wire, half-pin and hybrid and tested in axial compression, torsion, anteroposterior bending and mediolateral bending. Hybrid frames using 4 mm half-pins improved the anteroposterior stabilization of the short bone segment while maintaining axial characteristics similar to a three-wire frame. Increasing the bending stabilization will improve bone segment alignment while permitting axial micromotion beneficial to bone healing.

Stability of external circular fixation: a multi-variable biomechanical analysis.

OBJECTIVE: To determine how the manipulation of the parameters of fixation and components of the circular external frame could improve and maintain optimal stability of bone fragments. DESIGN: We performed a multi-parametric biomechanical analysis of the extrinsic parameters effecting bone fragment stabilization. Results of testing are presented as a percent change in stiffness due to the manipulation of frame components and their interaction with other fixation parameters. BACKGROUND: Although there have been investigations of the biomechanical characteristics of circular external fixation, they have been limited to either individual frame components or full frame comparisons. Therefore, these studies did not provide a comprehensive understanding of how the manipulation of circular fixator components influences bone fragment stability. METHODS: Mechanical testing was performed in three phases examining the effect of numerous components including ring diameter, wire angle, ring separation, etc. on axial, torsional and bending stiffness. RESULTS: For phase I (single ring) and phase II (double-ring block), ring diameter was the most significant factor affecting axial and torsional stiffness, while wire angle, ring separation, and their interaction had the most influence on bending stiffness. Phase III (two double-ring blocks) showed that ring positioning with respect to the osteotomy site had the most affect on bending and torsional stiffness while axial stiffness was non-linear and dependent upon the applied load. CONCLUSIONS: The stability of bone fragments within a circular external fixator is affected by manipulation of the parameters of fixation or individual components of the frame. The contribution of each component to overall bone fragment stability is dependent upon the mode of loading. The changes in overall stability of bone fragments are dependent not only on the individual frame components but also upon their interaction with other parameters of fixation. RELEVANCE: Understanding how the manipulation of individual frame components will affect overall bone fragment stabilization will allow the surgeon to better control the stability of bone fragments for each clinical situation.