Preference and Experience of Colonic Examination for Participants Presenting to Hospitals with a Positive Fecal Immunochemical Test Result.

PURPOSE: Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination. PATIENTS AND METHODS: Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience. RESULTS: The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups. CONCLUSION: Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more "comfortable" examination. Clinicians should therefore be aware of patients' potential preference for noninvasive colorectal examinations.

Assessment of tumor volume and density as a measure of the response of advanced hepatocellular carcinoma to sorafenib: Application of automated measurements on computed tomography scans.

BACKGROUND AND AIM: To better predict patient survival, we used automated tumor volume and density measurements to make an objective radiological assessment of the response of advanced hepatocellular carcinoma (HCC) to treatment with sorafenib. METHODS: Patients treated with sorafenib were identified retrospectively. Those who were diagnosed with Child-Pugh class A liver function, Barcelona-Clinic Liver Cancer stage C, and Eastern Cooperative Oncology Group performance status grade 0/1 were enrolled (n = 22). Reviews of contrast-enhanced computed tomography images were supported by the automated measurement of lesions using computer software. Treatment responses were assessed using volume and density criteria. Kaplan-Meier methods and multivariate Cox regression analysis were used to evaluate treatment responses and identify the most significant prognostic factors for overall survival (OS). RESULTS: After patients were dichotomized according to volume and density criteria, the median OS for those with an objective response (OR) (complete response + partial response) was 20.4 months and that for those with a non-OR (stable disease + progressive disease) was 9.3 months (P = 0.009). The best multivariate regression model for survival identified volume and density criteria (OR or non-OR) as a significant variable, along with baseline alpha-fetoprotein levels (log-rank test, P = 0.01). No other conventional criteria were identified as significant. CONCLUSIONS: Tumor volume and density assessment using automated lesion measurements may be an objective method of evaluating responses of advanced HCC to treatment with sorafenib.

Temporal subtraction of low-dose and relatively thick-slice CT images with large deformation diffeomorphic metric mapping and adaptive voxel matching for detection of bone metastases: A STARD-compliant article.

To evaluate the improvement of radiologist performance in detecting bone metastases at follow up low-dose computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm.Twelve patients with bone metastases (males, 5; females, 7; mean age, 64.8 ±â€Š7.6 years; range 51-81 years) and 12 control patients without bone metastases (males, 5; females, 7; mean age, 64.8 ±â€Š7.6 years; 51-81 years) were included, who underwent initial and follow-up CT examinations between December 2005 and July 2016. Initial CT images were registered to follow-up CT images by the algorithm, and TS images were created. Three radiologists independently assessed the bone metastases with and without the TS images. The reader averaged jackknife alternative free-response receiver operating characteristics figure of merit was used to compare the diagnostic accuracy.The reader-averaged values of the jackknife alternative free-response receiver operating characteristics figures of merit (θ) significantly improved from 0.687 for the readout without TS and 0.803 for the readout with TS (P value = .031. F statistic = 5.24). The changes in the absolute value of CT attenuations in true-positive lesions were significantly larger than those in false-negative lesions (P < .001). Using TS, segment-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the readout with TS were 66.7%, 98.9%, 94.4%, 90.9%, and 94.8%, respectively.The TS images can significantly improve the radiologist's performance in the detection of bone metastases on low-dose and relatively thick-slice CT.

Evaluation of the 95% limits of agreement of the volumes of 5-year clinically stable solid nodules for the development of a follow-up system for indeterminate solid nodules in CT lung cancer screening.

BACKGROUND: This study sought to evaluate the 95% limits of agreement of the volumes of 5-year clinically stable solid nodules for the development of a follow-up system for indeterminate solid nodules. METHODS: The volumes of 226 solid nodules that had been clinically stable for 5 years were measured in 186 patients (53 female never-smokers, 36 male never-smokers, 51 males with <30 pack-years, and 46 males with ≥30 pack-years) using a three-dimensional semiautomated method. Volume changes were evaluated using three methods: percent change, proportional change and growth rate. The 95% limits of agreement were evaluated using the Bland-Altman method. RESULTS: The 95% limits of agreement were as follows: range of percent change, from ±34.5% to ±37.8%; range of proportional change, from ±34.1% to ±36.8%; and range of growth rate, from ±39.2% to ±47.4%. Percent change-based, proportional change-based, and growth rate-based diagnoses of an increase or decrease in ten solid nodules were made at a mean of 302±402, 367±455, and 329±496 days, respectively, compared with a clinical diagnosis made at 809±616 days (P<0.05). CONCLUSIONS: The 95% limits of agreement for volume change in 5-year stable solid nodules may enable the detection of an increase or decrease in the solid nodule at an earlier stage than that enabled by a clinical diagnosis, possibly contributing to the development of a follow-up system for reducing the number of additional Computed tomography (CT) scans performed during the follow-up period.

Automatic digital quantification of bone marrow myeloma volume in appendicular skeletons - clinical implications and prognostic significance.

Multiple myeloma (MM) is a clonal plasma cell disorder originating in bone marrow. Whole body low-dose multidetector CT (MDCT) can depict bone marrow infiltration by myeloma cells into the adipose-rich fatty marrow of the appendicular skeleton. However, automated and objective volume measurement of bone marrow infiltration has not been established, and its clinical relevance remains unclear. We therefore developed novel CT post-processing software (MABLE software) and measured the total sum of CT values (cumulative CT value, cCTv) representing bone marrow infiltration, by combining volume and voxel-based CT values. The cCTv was greater in patients with symptomatic MM than in those with smouldering MM or monoclonal gammopathy of unknown significance. Patients with revised International Staging System (R-ISS) III had a higher cCTv than those with R-ISS I or II. Age, albumin, and M-protein levels independently predicted cCTv. Mixed graphical model analysis revealed direct relationships between cCTv and age or R-ISS. Tree-structured survival analysis and multivariate Cox analysis revealed that a cCTv greater than or equal to 4.4 was independently prognostic for overall survival. Anti-myeloma therapy reduced cCTv after treatment. These findings suggest that the automatically calculated cCTv reflects disease aggressiveness and is useful for accurate prognostic prediction in MM patients.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

Evaluation of a cloud-based local-read paradigm for imaging evaluations in oncology clinical trials for lung cancer.

BACKGROUND: Although tumor response evaluated with radiological imaging is frequently used as a primary endpoint in clinical trials, it is difficult to obtain precise results because of inter- and intra-observer differences. PURPOSE: To evaluate usefulness of a cloud-based local-read paradigm implementing software solutions that standardize imaging evaluations among international investigator sites for clinical trials of lung cancer. MATERIAL AND METHODS: Two studies were performed: KUMO I and KUMO I Extension. KUMO I was a pilot study aiming at demonstrating the feasibility of cloud implementation and identifying issues regarding variability of evaluations among sites. Chest CT scans at three time-points from baseline to progression, from 10 patients with lung cancer who were treated with EGFR tyrosine kinase inhibitors, were evaluated independently by two oncologists (Japan) and one radiologist (France), through a cloud-based software solution. The KUMO I Extension was performed based on the results of KUMO I. RESULTS: KUMO I showed discordance rates of 40% for target lesion selection, 70% for overall response at the first time-point, and 60% for overall response at the second time-point. Since the main reason for the discordance was differences in the selection of target lesions, KUMO I Extension added a cloud-based quality control service to achieve a consensus on the selection of target lesions, resulting in an improved rate of agreement of response evaluations. CONCLUSION: The study shows the feasibility of imaging evaluations at investigator sites, based on cloud services for clinical studies involving multiple international sites. This system offers a step forward in standardizing evaluations of images among widely dispersed sites.

Volume-based response evaluation with consensual lesion selection: a pilot study by using cloud solutions and comparison to RECIST 1.1.

RATIONALE AND OBJECTIVES: Lesion volume is considered as a promising alternative to Response Evaluation Criteria in Solid Tumors (RECIST) to make tumor measurements more accurate and consistent, which would enable an earlier detection of temporal changes. In this article, we report the results of a pilot study aiming at evaluating the effects of a consensual lesion selection on volume-based response (VBR) assessments. MATERIALS AND METHODS: Eleven patients with lung computed tomography scans acquired at three time points were selected from Reference Image Database to Evaluate Response to therapy in lung cancer (RIDER) and proprietary databases. Images were analyzed according to RECIST 1.1 and VBR criteria by three readers working in different geographic locations. Cloud solutions were used to connect readers and carry out a consensus process on the selection of lesions used for computing response. Because there are not currently accepted thresholds for computing VBR, we have applied a set of thresholds based on measurement variability (-35% and +55%). The benefit of this consensus was measured in terms of multiobserver agreement by using Fleiss kappa (κfleiss) and corresponding standard errors (SE). RESULTS: VBR after consensual selection of target lesions allowed to obtain κfleiss = 0.85 (SE = 0.091), which increases up to 0.95 (SE = 0.092), if an extra consensus on new lesions is added. As a reference, the agreement when applying RECIST without consensus was κfleiss = 0.72 (SE = 0.088). These differences were found to be statistically significant according to a z-test. CONCLUSIONS: An agreement on the selection of lesions allows reducing the inter-reader variability when computing VBR. Cloud solutions showed to be an interesting and feasible strategy for standardizing response evaluations, reducing variability, and increasing consistency of results in multicenter clinical trials.

Surface chemical approach to single-step measurement of antibody in human serum using localized surface plasmon resonance biosensor on microtiter plate system.

In clinical settings, serum antibody levels serve as markers of pathology. For example, antibodies related to autoimmune diseases are among the conventional targets in laboratory tests. Simple clinical tests can improve the efficacy of laboratory practice. This study describes a single-step, wash-free technique for optically detecting antibodies in human serum through the localized surface plasmon resonance (LSPR) of gold nanoparticles. As a proof-of-concept experiment, the amount of antibiotin dissolved in human serum was measured with a LSPR-based biosensor in a wash-free manner using a conventional 96-well microtiter plate and a plate reader. For an efficient surface modification of biosensors, zwitterionic copolymer was used as a scaffold on the gold nanoparticle surface to immobilize antigen and blocking reagent. Single-step, wash-free measurement of antibiotin in human serum was successfully achieved. In addition, nonspecific responses from serum contents were significantly reduced because both the copolymer and hydrophilic antigen reagent that we employed were composed of poly(ethylene oxide) spacer. Comparative experiments of the antigen-antibody reaction in serum to that in buffered solution revealed that serum is a favorable environment for the biological reaction. In conclusion, our gold-nanoparticle-based LSPR method may provide a rapid and simple way to measure the amount of antibody in serum quantitatively in clinical practice.

Single-step, label-free quantification of antibody in human serum for clinical applications based on localized surface plasmon resonance.

The amount of antibody in blood is an important measure of health status for making critical decisions in clinical practice. Here, we demonstrated a single-step, label-free, molecular diagnostic method based on localized surface plasmon resonance (LSPR) using standard 96-well microtiter plates. We improved the LSPR biosensor so that it can measure antibodies to blood group antigens in human serum with a single-step operation. First, we employed the ampholytic polymeric surface modification technique to present an efficient molecular scaffold on the sensor surface. Second, we selected the combination of an appropriate reference molecule against the antigen and a blocking agent to significantly reduce the variability of signal due to nonspecific responses of the unknown in the sample. Finally, we overcame the analytical difficulty arising from serum and achieved a single-step "wash-free" measurement of the amount of target antibody in human serum. FROM THE CLINICAL EDITOR: In this paper, a novel, single-step, label-free, molecular diagnostic method is discussed for antibody detection based on localized surface plasmon resonance using standard 96-well microtiter plates.

Anisotropic siloxane-based monolith prepared in confined spaces.

When bicontinuous gels are prepared via sol-gel method in a 2-dimensionally (2D) confined space, the gel skeletons in the vicinity of interface of a mold are elongated perpendicular to the interface. This phenomenon was attributed to the dynamic wetting of polymerizing siloxane phase onto the interface of the mold under gravity. In this paper, we report the successful preparation of monolithic columns with an oriented pillar structure in a variety of 2D confined spaces. Starting from a solution, which consists of methyltrimethoxysilane (MTMS), the macroporous structure is prepared in situ by a completely spontaneous process. In the oriented pillar structure, bicontinuous siloxane skeletons deformed or disappeared and most pillars are oriented along the direction of gravity. Gel morphologies with the pillar structure were examined by scanning electron microscopy (SEM) and laser scanning confocal microscopy (LSCM). Geometrical information on gel morphologies was numerically derived from the obtained 3D LSCM images.