Radiological criteria for selecting candidates for neoadjuvant chemotherapy for gastric cancer: an exploratory analysis from the PRODIGY study.

BACKGROUND: In this exploratory analysis from the PRODIGY study, we aimed to define the radiological criteria to identify patients with gastric cancer who may derive maximal clinical benefit from neoadjuvant chemotherapy. PATIENTS AND METHODS: There were 246 patients allocated to receive surgery followed by adjuvant S-1 (SC group) and 238 allocated to receive neoadjuvant chemotherapy (CSC group). As the PRODIGY's radiological method of lymph node (LN) evaluation considers short diameter and morphology (the size and morphology method), a method considering only short diameter was also employed. In the SC group, the correlation between radiologic and pathologic findings was analyzed. The hazard ratio (HR) for the progression-free survival (PFS) of the CSC group was analyzed in subgroups with different cT/N stages. RESULTS: cT4 disease showed a sensitivity of 85.6% for detecting pT4 and had a low proportion of pathologic stage (pStage) I disease (4.5%). Among the criteria determined by different cT/N stages by each method of LN positivity, those involving cT4Nany or cT4N + by both methods had a minimal proportion of pStage I disease (≤ 5%), while cT4Nany by both methods and cT4N + by the size and morphology method exhibited ≥ 75.9% sensitivity for detecting pStage III disease. The relative risk reduction in PFS of the CSC group was greatest in patients meeting the cT4Nany criterion defined by both methods (HR 0.67, 95% confidence interval 0.48-0.93). CONCLUSIONS: The cT4Nany criterion, regardless of the radiological method used for LN evaluation, may help select patients with resectable gastric cancer for neoadjuvant chemotherapy.

[Sternal fracture in growing children : A rare and often overlooked fracture? Documentation of four cases]. / Sternumfraktur im Wachstumsalter : Eine seltene oder häufig übersehene Fraktur? Dokumentation von 4 Fällen.

BACKGROUND: Sternal fractures in childhood are rare. The aim of the study was to investigate the accident mechanism, the detection of radiological and sonographical criteria and consideration of associated injuries. METHOD: In the period from January 2010 to December 2012 all inpatients and outpatients with sternal fractures were recorded according to the documentation. RESULTS: A total of 4 children aged 5-14 years with a sternal fracture were treated in 2 years, 2 children were hospitalized for pain management and 2 remained in outpatient care. CONCLUSION: Isolated sternal fractures in childhood are often due to typical age-related traumatic incidents. Ultrasonography is a useful diagnostic tool for fracture detection and radiography is the method of choice for visualization of the extent of the dislocation.

Effect of modified clivoaxial angle on surgical decision making and treatment outcomes in patients with Chiari malformation type 1.

Introduction: Chiari malformation type 1 (CM1), a complex pathological developmental disorder of the craniovertebral junction, is typically characterized by herniation of the cerebellar tonsils from the foramen magnum. Treatment using posterior fossa decompression alone without taking the ventral cervico-medullary compression into consideration may lead to unsatisfactory treatment outcomes. The current study evaluated the utility of the modified clivoaxial angle (MCAA) in assessing ventral compression and also examined its effect on treatment outcomes. Method: This retrospective study included 215 adult patients who underwent surgical treatment for CM1 at one medical center over a 10-year period. The following surgical techniques were used to decompress the posterior fossa: (a) PFD: bone removal only; (b) PFDwD: bone removal with duraplasty; and (c) CTR: cerebellar tonsil resection. The morphometric measurements of the craniovertebral junction (including MCAA) were recorded using preoperative images, and the postoperative clinical status was evaluated using the Chicago Chiari outcome scale (CCOS). Results: MCAA was positively correlated with the CCOS score and also independently predicted treatment outcome. To enable Receiver operating characteristic (ROC) curve analysis of CCOS scores, the patients were divided into three groups based on the MCAA cut-off values, as follows: (a) severe (n = 43): MCAA ≤ 126; (b) moderate (n = 86): 126 < MCAA ≤ 138; and (c) mild (n = 86): MCAA > 138. Group a exhibited severe ventral cervico-medullary compression (VCMC), and their CCOS scores for the PFD, PFDwD, and CTR groups were 11.01 ± 1.2, 11.24 ± 1.3, and 13.01 ± 1.2, respectively (p < 0.05). The CCOS scores increased with widening of the MCAA angle in all surgical groups (p < 0.05). Furthermore, patients with mild MCAA (>138°) exhibited 78% regression of syringomyelia, and this was significantly greater than that observed in the other groups. Discussion: MCAA can be used in the selection of appropriate surgical techniques and prediction of treatment outcomes, highlighting the importance of preoperative evaluation of ventral clivoaxial compression in patients with CM1.

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints.

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives.

Comparison of radiological criteria for hyperprogressive disease in response to immunotherapy.

Hyperprogressive disease (HPD) is a concerning paradoxical acceleration of cancer growth induced by immune drugs. The lack of standard radiological criteria makes its study challenging. We reviewed the literature and compared the main criteria for HPD proposed by Ferté, Le Tourneau, Garralda and Caramella to address this relevant unmet need in Immune-oncology. Among 182 consecutive patients with advanced cancer treated with immunotherapy in early-phase clinical trials, 71 with progressive disease at the first evaluation were eligible. HPD patients were studied regarding tumor growth dynamics and clinical impact. HPD occurred in 17 (23.9%), 17 (23.9%), 23 (32.4%) and 6 (8.4%) patients, as defined by Ferté, Le Tourneau, Garralda and Caramella, respectively. The strongest association was found between the Ferté and Le Tourneau criteria (Kappa = 0.61), and the Jaccard similarity index varied from 55% (Ferté and Le Tourneau) to 21% (Le Tourneau and Caramella). The Ferté and Le Tourneau criteria showed statistically significant differences between pre-baseline and post-baseline tumor growth rate in patients with HPD, which could not be confirmed with the Caramella and Garralda criteria. Significant differences in progression-free survival were observed between non-hyperprogressors and hyperprogressors, with all criteria. The proportion of patients that could not receive additional lines of therapy was higher in the HPD group. HPD is an immunotherapy-related acceleration of tumor growth kinetics, with a consequent negative clinical impact. Pre-baseline CT scans and tumor growth rate evaluations are required to identify HPD. Our analysis favors the use of the Le Tourneau method, as it captures adequately the HPD phenomenon and is more convenient to use.

Radiologically defining horizontal gaze using EOS imaging-a prospective study of healthy subjects and a retrospective audit.

BACKGROUND CONTEXT: As sagittal alignment of the cervical spine is important for maintaining horizontal gaze, it is important to determine the former for surgical correction. However, horizontal gaze remains poorly-defined from a radiological point of view. PURPOSE: The objective of this study was to establish radiological criteria to define horizontal gaze. STUDY DESIGN/SETTING: This study was conducted at a tertiary health-care institution over a 1-month period. PATIENT SAMPLE: A prospective cohort of healthy patients was used to determine the best radiological criteria for defining horizontal gaze. A retrospective cohort of patients without rigid spinal deformities was used to audit the incidence of horizontal gaze. OUTCOME MEASURES: Two categories of radiological parameters for determining horizontal gaze were tested: (1) the vertical offset distances of key identifiable structures from the horizontal gaze axis and (2) imaginary lines convergent with the horizontal gaze axis. MATERIALS AND METHODS: Sixty-seven healthy subjects underwent whole-body EOS radiographs taken in a directed standing posture. Horizontal gaze was radiologically defined using each parameter, as represented by their means, 95% confidence intervals (CIs), and associated 2 standard deviations (SDs). Subsequently, applying the radiological criteria, we conducted a retrospective audit of such radiographs (before the implementation of a strict radioimaging standardization). RESULTS: The mean age of our prospective cohort was 46.8 years, whereas that of our retrospective cohort was 37.2 years. Gender was evenly distributed across both cohorts. The four parameters with the lowest 95% CI and 2 SD were the distance offsets of the midpoint of the hard palate (A) and the base of the sella turcica (B), the horizontal convergents formed by the tangential line to the hard palate (C), and the line joining the center of the orbital orifice with the internal occipital protuberance (D). In the prospective cohort, good sensitivity (>98%) was attained when two or more parameters were used. Audit using Criterion B+D yielded compliance rates of 76.7%, a figure much closer to that of A+B+C+D (74.8%). From a practical viewpoint, Criterion B+D were most suitable for clinical use and could be simplified to the "3-6-12 rule" as a form of cursory assessment. Verbal instructions in the absence of stringent postural checks only ensured that ~75% of subjects achieved horizontal gaze. CONCLUSIONS: Fulfillment of Criterion B+D is sufficient to evaluate for horizontal gaze. Further criteria can be added to increase sensitivity. Verbal instructions alone yield high rates of inaccuracy when attempting to image patients in horizontal gaze. Apart from improving methods for obtaining radiographs, a radiological definition of horizontal gaze should be routinely applied for better evaluation of sagittal spinal alignment.

Proposed radiological criteria for pre-operative determination of resectability in peritoneal-based malignancies.

BACKGROUND: The selection of patients for cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy infusion (HIPEC) is important, and relies heavily on imaging. However, it has been reported that Computer Tomographic (CT) scans may only achieve a low sensitivity of 33% for peritoneal disease. We propose a set of radiological criteria for pre-operative determination of resectability of peritoneal disease in peritoneal-based malignancies and validate this in our cohort of patients. METHODS: A retrospective review of all patients who underwent laparotomy with a view for CRS and HIPEC, at the National Cancer Centre Singapore from January 2000 to April 2010, was performed. Intra-operative Peritoneal Cancer Index (PCI) scores were recorded. The pre-operative imaging was reviewed with a senior radiologist who was blinded, and recorded the radiological PCI scores (CT-PCI) and eight additional CT prognostic factors (CT-PF). The CT-PCI and CT-PF scores were then compared with the intra-operative findings to determine the radiological accuracy. The scores and the individual prognostic factors were then evaluated for their predictive ability for unresectability. RESULTS: Comparison of the CT-PCI and PCI scores showed a concordance correlation coefficient at 0.52 (95% CI 0.34-0.7). Accuracy was increased with the addition CT-PF. The presence of omental caking and ascites were predictors of unresectability. We propose a scoring system which is able to predict for unresectable disease with a specificity of 80% and a sensitivity of 62%. CONCLUSION: With our proposed criteria, and scoring system, the selection of patients for CRS and HIPEC can be improved, and unnecessary exploratory operations avoided.

Cavernous Sinus Invasion in Pituitary Adenomas: Systematic Review and Pooled Data Meta-Analysis of Radiologic Criteria and Comparison of Endoscopic and Microscopic Surgery.

BACKGROUND: Despite the substantial impact of cavernous sinus invasion (CSI) in pituitary adenoma surgery, its radiologic determination has been inconsistent and variable, and the role of endonasal endoscopic surgery has been unclear. This is a systematic review and pooled data meta-analysis of the literature to ascertain the best radiologic criteria for CSI and verify the efficacy and safety of an endonasal endoscopic approach. METHODS: We searched the MEDLINE database (1993-2015) to identify studies on radiologic criteria for CSI and endonasal surgery. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the studies included were reviewed for CSI criteria, gross total resection (GTR), endocrine remission, cranial nerve deficits, carotid injury, and other complications. RESULTS: The prevalence of CSI was 43% radiographically compared with 18% intraoperatively (P < 0.001). The radiologic criteria of inferolateral venous compartment obliteration and Knosp 3-4 had the highest correlation with intraoperative CSI and the lowest correlation with GTR. Microscopy had significantly overestimated intraoperative CSI compared with endoscopy (P < 0.001) for each Knosp grade. Endoscopy had significantly higher GTR than did microscopy particularly for Knosp 3-4 (47% vs. 21%; P = 0.001). Carotid injury and cranial nerve deficits occurred in 0.9% and 5%, respectively, with endoscopy. Among endoscopic series with CSI, GTR% showed significant correlation with number of patients in the series (P ≤ 0.01) but no correlation with complications, indicating the relative safety of endonasal endoscopy in experienced hands for removing tumors with CSI. CONCLUSIONS: Knosp 3-4 remains the best objective indicator of CSI. Microscopy tends to overestimate intraoperative CSI compared with endoscopy. Among pituitary adenomas with CSI, GTR in endoscopic series is higher than microscopy and improves with experience without significant additional morbidity.

Measuring spinal canal size in lumbar spinal stenosis: description of method and preliminary results.

BACKGROUND: Lumbar spinal stenosis is a pathological condition of the spinal channel with its concentric narrowing with presence of specific clinical syndrome. Absence of the clear unified radiological signs is the one of the basic problems of the lumbar spinal stenosis. PURPOSE: The authors seek to create method of assessment of the spinal canal narrowing degree, based on anatomical aspects of lumbar spinal stenosis. STUDY DESIGN: Development of diagnostic criteria based on analysis of a consecutive patients group and a control group. METHODS: Thirty seven patients (73 stenotic segments) with mean age 62,4 years old were involved in the study. Severity of clinical symptoms has been estimated by the measuring scales: Oswestry Disability Index (ODI) and Swiss Spinal Stenosis Questionnaire (SSQ). Mean number of the stenotic segments was 1.97. For all patients 8 radiological criteria have been measured. In the control group have been included 37 randomly selected patients (volunteers) in mean age of 53,4 years old without stenosis signs and narrowing of the spinal canal on the MRI imaging (73 segments total). Measurements were performed at the middle of intervertebral disc and facet joints level. RESULTS: For description of the state of spinal canal we offer the coefficient: ratio of the lateral canals total area to the cross-sectional area of the dural sac ("coefficient of stenosis"). Comparison of mean values of "coefficient of stenosis" for main and control groups showed statistically significant differences (t = -12,5; p < 0.0001). Strong statistically significant correlation with the ODI and SSS scales was revealed for the obtained coefficient (p <0.05). CONCLUSIONS: In our study new method of assessment of the spinal canal narrowing degree has been applied. Promising results have been obtained in a small group of patients. It is necessary to check the data on a large sample of recommendations for its clinical application.

WHOQOL-BREF Hindi questionnaire: Quality of life assessment in acetabular fracture patients.

BACKGROUND: The incidence of acetabular fractures in India has increased over the past years but so has the operating skills of pelvi-acetabular trauma surgeons. The outcomes of surgical management need to be assessed so as to be able to devise proper treatment plan and execute the same during and after surgery, which in turn requires assessment of quality of life indices as well as functional scores. While there are studies assessing Harris Hip scores (HHS) and world health organization quality of life BREF (WHOQOL BREF) in the western population there is no study which assesses the same in Indian population. We designed this study to evaluate and define reference values for use of WHOQOL BREF Hindi scores in QOL Assessment in patients with acetabular fractures and to assess the relationship between it and HHS. MATERIALS AND METHODS: 118 patients with acetabular fractures who were treated surgically were included in this retrospective study. Assessment of reduction quality (Matta's radiological criteria), clinical outcome (HHS) and functional outcome (WHOQOL-BREF score) were done. The affect of age, gender, fracture displacement, hip dislocation, delay in surgery and associated injury on the clinical and functional outcome was evaluated. RESULTS: The mean HHS was 90.65 (42-100) which showed an overall good to excellent outcome in 78.8% cases. WHOQOL-BREF Hindi score of domain-one was 63.06 ± 20.31 (13-94), of domain-two was 58.22 ± 19.57 (13-100), of domain-three was 70.49 ± 17.92 (13-100) and of domain-four was 64.48 ± 18.46 (13-100), which showed significant functional deficit in domain-one (P = 0.0001) and domain-two (P = 0.0001) but not in domain-three (P = 0.458) and domain-four (P = 0.722) when compared to score of general healthy population. The domain scores of general population norms were achieved in 59.3%, 61.9%, 69.5% and 66.1% cases in domain one, two, three and four respectively. CONCLUSIONS: Based on these results one can conclude that WHOQOL-Hindi questionnaire is good enough for assessment of QOL in addition to clinical measures in acetabular fracture patients.