Clinical utility of geriatric assessment tools in older patients with gastrointestinal cancer.

Background: Geriatric 8 (G8) and instrumental activities of daily living (IADL) are recommended to predict overall survival (OS) or risk of serious adverse events (SAEs) in older cancer patients. However, the clinical utility is relatively unknown in older patients suffering malnutrition with gastrointestinal (GI) cancer, including gastric cancer (GC) and pancreatic cancer (PC). Materials and methods: We retrospectively included patients aged ≥65 years with GC, PC, and colorectal cancer (CRC) who received a G8 questionnaire at first visit from April 2018 to March 2020. The associations between G8/IADL and safety or OS were assessed in patients with advanced/unresectable tumors. Results: Of 207 patients (median age: 75 years), the median G8 score was 10.5 and normal G8 score rate was 6.8%. Both the median G8 score and normal G8 (>14) score rate numerically increased in the order of GC < PC < CRC. There was no clear association between the G8 standard cutoff value of 14 and SAEs or OS. However, OS was significantly longer in patients with G8 >11 than in those with G8 ≤11 (19.3 vs. 10.5 months, p = 0.0017). Furthermore, OS was significantly better in patients with normal IADL than in those with abnormal IADL (17.6 vs. 11.4 months, p = 0.049). Conclusion: The G8 cutoff value of 14 would not be clinically useful in patients with GI cancer for predicting OS or SAEs; however, the cutoff value of 11 and IADL may be useful to predict OS for older patients with GI cancers including GC and PC.

Automated assessment of Ki-67 in breast cancer: the utility of digital image analysis using virtual triple staining and whole slide imaging.

AIMS: Precise evaluation of proliferative activity is essential for the stratified treatment of luminal-type breast cancer (BC). Immunohistochemical staining of Ki-67 has been widely used to determine proliferative activity and is recognised to be a useful prognostic marker. However, there remains discussion concerning the methodology. We aimed to develop an automated and reliable Ki-67 assessment approach for invasive BC. MATERIALS AND RESULTS: A retrospective study was designed to include two cohorts consisting of 152 and 261 consecutive patients with luminal-type BC. Representative tissue blocks following surgery were collected, and three serial sections were stained automatically with Ki-67, pan-cytokeratin and p63. The whole slides were scanned digitally and aligned using VirtualTripleStaining - an extension to the VirtualDoubleStaining™ technique provided by Visiopharm software. The aligned files underwent automated invasive cancer detection, hot-spot identification and Ki-67 counting. The automated scores showed a significant positive correlation with the pathologists' scores (r = 0.82, P < 0.0001). Among selected patients with curative surgery and standard adjuvant therapies (n = 130), the digitally assessed low Ki-67 group (<20%) demonstrated a significantly better prognosis (breast cancer-specific survival, P = 0.030; hazard ratio = 0.038) than the high Ki-67 group. CONCLUSIONS: Digital image analysis yielded similar results to the scores determined by experienced pathologists. The prognostic utility was verified in our cohort, and an automated process is expected to have high reproducibility. Although some pitfalls were confirmed and thus need to be monitored by laboratory staff, the application could be utilised for the assessment of BC.

Pulmonary flow assessment by phase-contrast MRI can predict short-term mortality of fibrosing interstitial lung diseases.

BACKGROUND: Phase-contrast magnetic resonance imaging (PC-MRI) can determine pulmonary hemodynamics non-invasively. Pulmonary hypertension causes changes in pulmonary hemodynamics and is a factor for acute exacerbation and death in interstitial lung diseases (ILD). PURPOSE: To determine associations between pulmonary hemodynamics measured by PC-MRI and short-term mortality in patients with ILD. MATERIAL AND METHODS: Pulmonary hemodynamics, measured by PC-MRI in 43 patients with ILD, were reviewed retrospectively. Evaluation parameters included heart rate, right cardiac output, average flow, average velocity, acceleration time, acceleration volume (AV), maximal change in flow rate during ejection (M), M/AV, maximum area, minimum area, and relative area change in the pulmonary artery (PA). All causes of death within one year from the day of the MRI examination were assessed by reviewing medical records. Associations between evaluation parameters and outcome were determined by univariate and multivariate Cox regression analysis. RESULTS: Six patients (13.9%) died by the one-year follow-up. Age (hazard ratio [HR] 1.116, 95% confidence interval [CI] 1.015-1.269), average flow (HR 0.932, 95% CI 0.870-0.984), average velocity (HR 0.778, 95% CI 0.573-0.976), right cardiac output (HR 0.870, 95% CI 0.758-0.967), AV (HR 0.840, 95% CI 0.669-0.985), M/AV (HR 1.008, 95% CI 1.001-1.014), and PA relative area change (HR 0.715, 95% CI 0.459-0.928) predicted death in univariate Cox analysis. Multivariate Cox analysis showed decreased right cardiac output (HR 0.547, 95% CI 0.160-0.912) and decreased PA relative area change (HR 0.538, 95% CI 0.177-0.922) were independently associated with death. CONCLUSION: Reduction in right cardiac output and decreased PA relative area change, detected by PC-MRI, were associated with increased mortality in ILD.

Performance of a time-resolved IR facility for assessment of protonation states and polarity changes in carboxyl groups in a large membrane protein, mammalian cytochrome c oxidase, under turnover conditions in a sub-millisecond time resolution.

Time-resolved IR analyses for the protonation and polarity changes of carboxyl groups involved in proton pump enzymes under turnover conditions are indispensable for elucidation of their proton-pump mechanisms. We have developed a new time-resolved infrared facility by introducing a flow system for transferring highly concentrated and thus viscous protein solution to a thin (50 µm) flow cell equipped in a highly sensitive IR spectrometer constructed with the femtosecond mid-IR pulse laser with spectral width of 350 cm-1 as an IR white light source equipped with multi-channel MCT detector. This facility equipped with O2 supply system enables the sub-millisecond time scale infrared measurements of the O2 reduction coupled with proton pumping by bovine cytochrome c oxidase (CcO) initiated by CO-flash photolysis in the COOH (1725-1770 cm-1) region with the accuracy of about 10 µO.D. under the background O.D. of 1. The facility identifies a band intensity change at ~1744 cm-1 assignable to protonation of a carboxyl group coupled with a single electron transfer to the O2 reduction center within 1 ms after initiation of the reaction. The results suggest that the facility detects protonation of a single carboxyl group included in large proteins like as CcO (210 kDa). The present facility sensitively identifies also polarity changes in COOH group by detecting shifts of the bands near 1750 cm-1 and 1760 cm-1, without significant intensity changes. These findings show the performance of this facility sufficiently high for providing crucial information for understanding the proton transferring mechanisms of protein carboxyl groups.

Diagnostic certainty of idiopathic pulmonary fibrosis/usual interstitial pneumonia: The effect of the integrated clinico-radiological assessment.

OBJECTIVE: To reevaluate idiopathic pulmonary fibrosis (IPF) cases which had surgical lung biopsy (SLB) for diagnosis of usual interstitial pneumonia (UIP), and examine the influence of computed tomography (CT) findings and clinical information based on diagnostic certainty. METHODS: Ninety-five cases with multidisciplinary diagnoses of IPF were identified from eight institutions. All cases had SLB. Two expert chest radiologists and five expert pulmonologists used a 5-point scale to grade their level of certainty in the diagnosis of a radiological pattern of UIP or a clinical diagnosis of IPF (level 1 "definitely no" to level 5 "definitely yes"). Radiologists independently evaluated thin-section CT images and pulmonologists independently assessed clinical information. The two groups then discussed their diagnosis to obtain a final consensus, and listed alternative diagnoses. Changes in the level of certainty during the diagnostic process were investigated. RESULTS: The level of certainty for IPF was judged as low (level 1 or 2) in 32 cases (34%) by radiologists and in three cases (3%) by pulmonologists; in the final consensus 39 cases (41%) were judged as low. Chronic hypersensitivity pneumonitis (CHP), interstitial pneumonia associated with collagen tissue diseases (CTD-IP), and idiopathic nonspecific interstitial pneumonia (idiopathic NSIP) were listed as alternative diagnoses. CONCLUSIONS: In this retrospective series, some cases that had UIP confirmed on SLB for IPF diagnosis were classified into a low-level certainty group by expert chest radiologists and pulmonologists. When a diagnosis of IPF is made, the possibility of CHP, CTD-IP, and idiopathic NSIP must be also considered.

Pulmonary Aluminosis Diagnosed with In-air Microparticle Induced X-ray Emission Analysis of Particles.

We herein present a case of pulmonary aluminosis diagnosed with in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis. The diagnosis of pulmonary aluminosis was supported by the occupational exposure to aluminum, ground glass opacity and ill-defined centrilobular nodular opacities seen in high resolution CT, and respiratory bronchioles accompanied by pigmented dust by histological examination by in-air micro-PIXE analysis of the lung tissues. The possibility of developing this rare condition should not be underestimated in workers at high-risk jobs. This is an important report showing the usefulness of an in-air micro-PIXE analysis for the early diagnosis of aluminosis.

Assessment of prognosis of patients with idiopathic pulmonary fibrosis by computer-aided analysis of CT images.

PURPOSE: To present the Gaussian Histogram Normalized Correlation (GHNC) system, to quantify the extent of disease on computed tomography (CT) images of idiopathic pulmonary fibrosis (IPF), and to assess its utility by comparing the radiologist' scoring and prognosis. MATERIALS AND METHODS: GHNC was used to analyze baseline thin-section CT images (30-60images per patients) of 40 patients with IPF. It classified the CT lung field into normal (N), ground-glass opacities (G), consolidation (C), emphysema (E) and fibrosis (F) patterns [the latter was also subdivided into reticular (F1) and honeycomb (F2) patterns], then the relative lung volume and relative each pattern volume (area multiplied by slice thickness and interval and divided by predicted total lung capacity) were estimated. The radiologists estimated the area of these patterns on 4 slices per patient; the average was regarded as total extent of each pattern. We compared the estimates determined by radiologists and GHNC with pulmonary function tests, and used Cox regression analysis to examine the relationships between the volumes and patient survival. RESULTS: The area of each pattern measured by GHNC correlated significantly with that estimated by the radiologist on 160 images (P<0.001, each). The volumes of N-pattern and F-patterns are measured by GHNC correlated with carbon monoxide diffusing capacity.During the follow-up (mean 49 mo), 24 patients died. Relative lung volume, N-pattern, F-pattern and F2-pattern correlated with survival in univariate analysis. Multivariate analysis identified F2-pattern volume by GHNC (P=0.034) as a significant predictor of survival. CONCLUSIONS: The GHNC provides automatic measurement of volume of fibrosis. The F2-pattern on CT can predict prognosis of patients with IPF.