P-OGC26 Learning curves in minimally invasive esophagectomy- a systematic review and evaluation of benchmarking parameters

Background Minimally invasive techniques are increasingly used in the treatment of esophageal cancer. The learning curve for minimally invasive oesophagectomy (MIO) is variable and can impact on patient outcomes. The aim of this study was to review the current evidence on learning curves in MIO and identify which parameters are used for benchmarking. Methods A search of the major reference databases (PubMed, Medline, Cochrane) was performed with no time limits up to February 2020. Results were screened in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if an assessment of the learning curve was reported on, regardless of which (if any) statistical method was used. Results Twenty-nine studies comprising 3741 patients were included. Twenty-two studies reported on a combination of thoracoscopic, hybrid and total MIO, 6 studies reported robotic assisted MIO (RAMIE) alone and 1 study evaluated both RAMIE and thoracoscopic esophagectomies. Operating time was the most frequently used parameter to determine learning curve progression (23/39 studies), with number of resected lymph nodes, morbidity and blood loss also frequently used. Learning curves were found to plateau at 7-60 cases for thoracoscopic esophagectomy, 12-175 cases for total and thoracoscopic/hybrid esophagectomy and 9-85 cases for RAMIE. Conclusions Multiple parameters are employed to gauge MIO learning curve progression. However, there are no validated or approved sets of outcomes. Further work is required to determine the optimum parameters that should be utilised to ensure best patient outcomes and required length of proctoring.

Potential Muscle-Related Biomarkers in Predicting Curve Progression to the Surgical Threshold in Adolescent Idiopathic Scoliosis—A Pilot Proteomic Study Comparing Four Non-Progressive vs. Four Progressive Patients vs. A Control Cohort

Previous studies have reported abnormal muscle morphology and functions in patients with adolescent idiopathic scoliosis (AIS). To answer whether such abnormalities could be reflected in their circulation and their clinical implication for predicting curve progression to the surgical threshold, this preliminary study explored the presence of baseline muscle-related proteins and their association with curve progression. Plasma samples were collected at the first clinical visit for AIS, with patients divided into non-progressive or progressive groups (N = four and four) according to their Cobb angle in six-year follow-ups, with age- and sex-matched healthy subjects (N = 50). Then, the samples were subjected to isobaric tags for relative and absolute quantitation (iTRAQ) for global comparison of untargeted protein expression. Seventy-one differentially expressed proteins (DEPs) were found elevated in progressive AIS. Functional analysis showed that 18 of these are expressed in muscles and play an essential role in muscle activities. Among the muscle-related DEPs, α-actin had the highest fold change in progressive/non-progressive groups. This preliminary study firstly suggested higher circulating levels of muscle structural proteins in progressive AIS, indicating the likelihood of structural damage at the microscopic level and its association with progression to the surgical threshold. Further studies with larger sample sizes are warranted to validate these novel candidates for early diagnosis and predicting progression.

Accounting for Biomechanical Measures from Musculoskeletal Simulation of Upright Posture Does Not Enhance the Prediction of Curve Progression in Adolescent Idiopathic Scoliosis

A major clinical challenge in adolescent idiopathic scoliosis (AIS) is the difficulty of predicting curve progression at initial presentation. The early detection of progressive curves can offer the opportunity to better target effective non-operative treatments, reducing the need for surgery and the risks of related complications. Predictive models for the detection of scoliosis progression in subjects before growth spurt have been developed. These models accounted for geometrical parameters of the global spine and local descriptors of the scoliotic curve, but neglected contributions from biomechanical measurements such as trunk muscle activation and intervertebral loading, which could provide advantageous information. The present study exploits a musculoskeletal model of the thoracolumbar spine, developed in AnyBody software and adapted and validated for the subject-specific characterization of mild scoliosis. A dataset of 100 AIS subjects with mild scoliosis and in pre-pubertal age at first examination, and recognized as stable (60) or progressive (40) after at least 6-months follow-up period was exploited. Anthropometrical data and geometrical parameters of the spine at first examination, as well as biomechanical parameters from musculoskeletal simulation replicating relaxed upright posture were accounted for as predictors of the scoliosis progression. Predicted height and weight were used for model scaling because not available in the original dataset. Robust procedure for obtaining such parameters from radiographic images was developed by exploiting a comparable dataset with real values. Six predictive modelling approaches based on different algorithms for the binary classification of stable and progressive cases were compared. The best fitting approaches were exploited to evaluate the effect of accounting for the biomechanical parameters on the prediction of scoliosis progression. The performance of two sets of predictors was compared: accounting for anthropometrical and geometrical parameters only; considering in addition the biomechanical ones. Median accuracy of the best fitting algorithms ranged from 0.76 to 0.78. No differences were found in the classification performance by including or neglecting the biomechanical parameters. Median sensitivity was 0.75, and that of specificity ranged from 0.75 to 0.83. In conclusion, accounting for biomechanical measures did not enhance the prediction of curve progression, thus not supporting a potential clinical application at this stage.

Longitudinal scoliosis behavior in Chiari malformation with and without syringomyelia

OBJECTIVE The objective of this study was to understand the natural history of scoliosis in patients with Chiari malformation type I (CM-I) with and without syringomyelia. METHODS A retrospective review of data was conducted. Patients with CM-I were identified from a cohort of 14,118 individuals age 18 years or younger who had undergone MRI over an 11-year period at the University of Michigan. Patients eligible for study inclusion had a coronal curve ≥ 10° on radiography, associated CM-I with or without syringomyelia, and at least 1 year of clinical follow-up prior to any surgery. Curve magnitude at initial diagnosis, prior to posterior fossa decompression (PFD; if applicable), and at the last follow-up (prior to any surgical correction of scoliosis) was recorded, and clinical and radiographic characteristics were noted. The change in curve magnitude by 10° was defined as curve progression (increase by 10°) or regression (decrease by 10°). RESULTS Forty-three patients met the study inclusion criteria and were analyzed. About one-third (35%) of the patients presented with symptoms attributed to their CM-I. The mean degree of scoliosis at presentation was 32.6° ± 17.7°. Twenty-one patients (49%) had an associated syrinx. The mean tonsil position below the level of the foramen magnum was 9.8 ± 5.8 mm. Patients with a syrinx were more likely to have a curve > 20° (86% vs 41%, p = 0.002). Curve magnitude remained stable (≤ ±10°) in 77% of patients (33/43), progressed in 16% (7/43), and regressed in 7% (3/43). Mean age was higher (14.8 ± 0.59 years) among patients with regressed curves (p = 0.026). All regressed curves initially measured ≤ 20° (mean 14° ± 5.3°), and none of the patients with regressed curves had a syrinx. The change in curve magnitude was statistically similar in patients with (7.32° ± 17.7°) and without (5.32° ± 15.8°) a syrinx (p = 0.67). After a mean follow-up of 3.13 ± 2.04 years prior to surgery, 27 patients (63%) ultimately underwent posterior fossa or scoliosis correction surgery. For those who eventually underwent PFD only, the rate of change in curve magnitude prior to surgery was 0.054° ± 0.79°. The rate of change in curve magnitude was statistically similar before (0.054° ± 0.79°) and after (0.042° ± 0.33°) surgery (p = 0.45) for patients who underwent PFD surgery only. CONCLUSIONS The natural history of scoliosis in the presence of CM-I is variable, though most curves remained stable. All curves that regressed were ≤ 20° at initial diagnosis, and most patients in such cases were older at scoliosis diagnosis. Patients who underwent no surgery or PFD only had similar profiles for the change in curve magnitude, which remained relatively stable overall, as compared to patients who underwent PFD and subsequent fusion, who demonstrated curve progression. Among the patients with a syrinx, no curves regressed, most remained stable, and some progressed. Understanding this variability is a first step toward building a prediction model for outcomes for these patients.

Alternate In-Brace and Out-of-Brace Radiographs Are Recommended to Assess Brace Fitting and Curve Progression With Adolescent Idiopathic Scoliosis Follow-Up

Study Design: Retrospective cohort study. Objective: To determine the prevalence of missed curve progression in patients with adolescent idiopathic scoliosis (AIS) undergoing brace treatment with only in-brace follow-up radiographs, and to provide recommendations on when in-brace and out-of-brace should be obtained during follow-up. Methods: 133 patients who had documented clinically significant curve progression during brace treatment or only when an out-of-brace radiograph were studied. Of these, 95 patients (71.4%) had curve progression noted on in-brace radiographs while 38 patients (28.6%) showed curve progression only after brace removal. We analyzed differences in age, sex, curve types, Risser stage, months after menarche, standing out-of-brace Cobb angle, correction rate, and flexibility rate between the groups. Multivariate logistic regression was performed to determine factors contributing to curve progression missed during brace treatment. Results: There were no differences in initial Cobb angle between out-of-brace and in-brace deterioration groups. However, the correction rate was higher (32.7% vs 25.0%; P = .004) in the in-brace deterioration group as compared to the out-of-brace deterioration group. A lower correction rate was more likely to result in out-of-brace deterioration (OR 0.970; P = .019). For thoracic curves, higher flexibility in the curves was more likely to result in out-of-brace deterioration (OR 1.055; P = .045). For double/triple curves, patients with in-brace deterioration had higher correction rate (OR 0.944; P = .034). Conclusions: Patients may develop curve progression despite good correction on in-brace radiographs. Those with higher flexibility and suboptimal brace fitting are at-risk. In-brace and out-of-brace radiographs should be taken alternately for brace treatment follow-up.

Should L3 be selected as the lowest instrumented vertebra in patients with Lenke type 5C adolescent idiopathic scoliosis whose lowest end vertebra is L4?

OBJECTIVE L3 is most often selected as the lowest instrumented vertebra (LIV) to conserve mobile segments in fusion surgery; however, in cases with the lowest end vertebra (LEV) at L4, LIV selection as L3 could have a potential risk of correction loss and coronal decompensation. This study aimed to compare the clinical and radiographic outcomes depending on the LEV in adolescent idiopathic scoliosis (AIS) patients with Lenke type 5C curves. METHODS Data from 49 AIS patients with Lenke type 5C curves who underwent selective thoracolumbar/lumbar (TL/L) fusion to L3 as the LIV were retrospectively analyzed. The patients were classified according to their LEVs into L3 and L4 groups. In the L4 group, subanalysis was performed according to the upper instrumented vertebra (UIV) level toward the upper end vertebra (UEV and 1 level above the UEV [UEV+1] subgroups). Radiographic parameters and clinical outcomes were compared between these groups. RESULTS Among 49 patients, 32 and 17 were in the L3 and L4 groups, respectively. The L4 group showed a lower TL/L curve correction rate and a higher subjacent disc angle postoperatively than the L3 group. Although no intergroup difference was observed in coronal balance (CB), the L4 group showed a significantly higher main thoracic (MT) and TL/L curve progression during the postoperative follow-up period than the L3 group. In the L4 group, the UEV+1 subgroup showed a higher absolute value of CB at 2 years than the UEV subgroup. CONCLUSIONS In Lenke type 5C AIS patients with posterior selective TL/L fusion to L3 as the LIV, patients with their LEVs at L4 showed postoperative MT and TL/L curve progression; however, no significant differences were observed in global alignment and clinical outcome.

Lower WNT16 expression in patients with adolescent idiopathic scoliosis – potential link to lower bone mass in AIS?

Adolescent Idiopathic Scoliosis (AIS) occurs during pubertal rapid growth period and is closely associated with low bone mass. The underlying mechanisms for systemic low bone mass in AIS remains unclear. Wnt signalling pathway is one of the important pathways regulating bone metabolism and influencing bone strength, its family member Wnt16 associates with lower bone mineral density (BMD) in late adulthood, and plays key regulatory role in determining cortical bone quality in adult mice. Our randomized control trial have reported vitamin D (VitD) supplementation significantly improved bone mass and reduced the risk of curve progression in AIS. A case-control study and animal study were employed to answer if WNT16 is associated with the abnormal bone quality in AIS and if the effect of VitD supplementation is associated with Wnt16, respectively. A cohort of 161 AIS and control female subjects were recruited for measurement of anthropometric parameters, bone qualities, and circulating Wnt16 level. In animal study, WT and Wnt16 gKO mice were both subjected to special VitD diet from week 4 and terminated at week 7 and 10 for samples harvesting. AIS showed significantly lower BMD, circulating WNT16 level, and elevated serum level of type I procollagen N-terminal propeptide. Wnt16 gKO mice demonstrated lower cortical bone density compared with WT mice from week 7 of age and Wnt16 gKO were less prone to cortical bone loss induced by high dosage VitD diet. Further study on the biological role of WNT16 and crosstalk with VitD metabolism on bone qualities is warranted which might shed light on prognostic gene of osteopenia and new perspectives for potential target to prevent curve progression.

Effect of Spinal Bracing on Curve Magnitude in Coronal and Axial Planes in Adolescent Scoliosis Utilising EOS Imaging.

Purpose. This study aimed to investigate the efficacy of spinal bracing in treating progressive scoliosis deformity utilizing EOS (bi-planer) imaging and SterEOS reconstruction software. Methods. EOS images of scoliosis patients being treated with bracing were obtained both in and out of their brace. These images were processed using SterEOS software to allow 3D representation, which was then compared to traditional coronal 2D parameters. Between January 2019 and January 2020, 29 patients were recruited for participation. Of these participants, 25 had a single episode of EOS imaging out of and in their brace. Additionally, 19 of the 25 participants had further episodes of EOS imaging within the study period, separated by mean 144+/-44 days. This allowed a total of 44 EOS single scan episodes for parameter analysis out of, and in the brace. Longitudinal analysis was also performed on the 19 patients who had sequential scans.Results. Participants were mean 13.8±1.1 years old at the first scan. Coronal 2D parameters, specifically Cobb Angle measurement, were accurately reproducible with SterEOS 3D measurements. Across all EOS scans (n=44) the mean major coronal curve measurement was 42.3±13.3° out of brace and 37.2±13.8° in the brace. This produced a mean correction of 4.6±4.4° (p<0.05). The correction achieved in this cohort with bracing appeared more modest than those reported in previous studies using traditional 2D coronal curve measurements1–3. The mean axial vertebral rotation (AVR) was 10.6±7.1° out of the brace and 9.6±6.8° in the brace, with a mean correction of 1.4±5.3°(p=0.14). The current study results suggested no significant change in axial vertebral rotation with brace treatment. Notably, in 17 of the 44 AVR measured, the differences were negative. That is, the AVR worsened in the brace. There was a significant moderate correlation between 3D coronal Cobb angle measured and AVR measured out of the brace for all curves. However, the change in Cobb and change in AVR with bracing did not correlate.Over sequential EOS episodes (n=19), there appeared no significant progression of 3D parameters, interpreted as the brace preventing curve progression.Conclusions. There appeared to be a consistent reduction in the scoliosis Cobb angle of the major curve with brace treatment. AVR demonstrated no significant change with bracing, with instances of worsening of AVR in the brace, which was not reflected by Cobb angle measurement. Despite this, bracing appears to have been effective with limited curve progression in sequential scans, though not in the anticipated manner of immediate in-brace curve correction.