Evaluation of Breast Edema Findings at T2-weighted Breast MRI Is Useful for Diagnosing Occult Inflammatory Breast Cancer and Can Predict Prognosis after Neoadjuvant Chemotherapy.

Background Prediction of occult inflammatory breast cancer (IBC) and breast cancer prognosis based on breast edema findings on T2-weighted MRI scans, even for patients without clinical signs of IBC, would be useful in both pretreatment planning and prognosis and may elucidate the underlying biologic mechanisms. Purpose To evaluate whether classification of breast edema on T2-weighted MRI scans is useful for predicting the prognosis of patients with breast cancer treated with neoadjuvant chemotherapy (NAC). Materials and Methods A retrospective evaluation was performed of women with breast cancer who underwent breast MRI and were treated with NAC between January 2011 and December 2018. Breast edema on T2-weighted images was scored on a scale of 1 to 4, as follows: (a) breast edema score (BES) 1, no edema; (b) BES 2, peritumoral edema; (c) BES 3, prepectoral edema; and (d) BES 4, subcutaneous edema (suspicious for occult IBC). Clinically evident IBC was classified as BES 5 (without MRI). The log-rank test was performed, and hazard ratios were calculated using the Cox hazard model to evaluate associations between BES and progression-free survival (PFS) and overall survival (OS). PFS rate at 100 months after initiation of therapy was also evaluated. Results Of 408 patients (median age, 53 years; range, 28-80 years), 65 (16%) had a recurrence and 27 (7%) died. The log-rank test revealed differences in PFS for BES 4 versus 1, BES 5 versus 1, BES 5 versus 2, and BES 5 versus 3 (adjusted P < .05 for all). PFS rates for BES 1-5 were 0.92, 0.85, 0.80, 0.62, and 0.58, respectively, and the corresponding OS rates at 100 months were 0.98, 0.91, 0.92, 0.77, 0.86, respectively. Conclusion Classification of breast edema findings on T2-weighted MRI scans using a breast edema score was related to the prognosis of patients after neoadjuvant chemotherapy. © RSNA, 2021 Online supplemental material is available for this article.

Randomized study of prevention of gastrointestinal toxicities by nutritional support using an amino acid-rich elemental diet during chemotherapy in patients with esophageal cancer (KDOG 1101).

BACKGROUND: This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. METHODS: The inclusion criteria were as follows: (1) esophageal squamous cell carcinoma, (2) stage IB-IV, (3) schedule to receive docetaxel, cisplatin, and 5-fluorouracil (DCF chemotherapy), (4) 20-80 years old, (5) performance status of 0-2, (6) oral intake ability, and (7) written informed consent. Patients were divided into two groups: the elemental supplementary group and the non-supplementary group. Patients received ELENTAL® (160 g/day) orally 9 weeks after the start of chemotherapy. Primary endpoint was the incidence of grade 2 or higher gastrointestinal toxicity according to the Common Terminology Criteria for Adverse Events, version 4.0. Secondary endpoints were the incidence of all adverse events and the evaluation of nutritional status. RESULTS: Thirty-six patients in the elemental supplementary group and 35 patients in the non-supplementary group were included in the analysis. The incidence of grade 2 or higher gastrointestinal toxicity and all grade 3 or 4 adverse events did not differ significantly between the groups. In the elemental supplementary group, the body weight (p = 0.057), muscle mass (p = 0.056), and blood levels of transferrin (p = 0.009), total amino acids (p = 0.019), and essential amino acids (p = 0.006) tended to be maintained after chemotherapy. CONCLUSION: Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer.

Japanese version of The Cancer Genome Atlas, JCGA, established using fresh frozen tumors obtained from 5143 cancer patients.

This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single-center study called "High-tech Omics-based Patient Evaluation" or "Project HOPE" conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole-exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed "Shizuoka Multi-omics Analysis Protocol" developed in-house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non-cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.

Is the presence of edema and necrosis on T2WI pretreatment breast MRI the key to predict pCR of triple negative breast cancer?

PURPOSE: Given that a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic factor, evaluating pretreatment imaging findings is important. Outcomes for triple negative breast cancer (TNBC) vary with the histological classification, indicating that this classification is clinically significant. In this study, we focus on the most common histological subtype of TNBC, invasive carcinoma of no special type (NST), to evaluate whether intramammary edema (intra-E) and intratumoral necrosis (intra-N) on T2-weighted magnetic resonance imaging (T2WI) is a useful predictor of pCR. METHOD: We retrospectively included patients with biopsy-diagnosed TNBC-NST who received NAC between January 2014 and December 2017. Intra-E and intra-N were evaluated on T2WI before NAC. We grouped intra-E into no edema, peritumoral edema, prepectoral edema, and subcutaneous edema, and we defined intra-N as water-like signal intensity without enhancement on T2WI. We also evaluated tumor size, Ki-67 expression, and histological/nuclear grade, as well as their correlation with intra-E and intra-N. RESULTS: Fifty-seven patients with TNBC-NST were enrolled. There was no correlation with the rate of pCR and the presence of either intra-E or intra-N before NAC. Only intra-E and tumor size showed a positive correlation. CONCLUSIONS: In patients with TNBC-NST, intra-E and intra-N did not correlate with pCR, but intra-E did positively correlate with tumor size. NST may exhibit a greater response to NAC, regardless of whether intra-E or intra-N is present or not on the pretreatment MRI. KEY POINTS: • Pathological complete response in TNBC-NST had no correlation with intramammary edema or intratumoral necrosis. • NAC may be justified in TNBC-NST even in the presence of edema or necrosis. • The extension of edema correlated with tumor size of TNBC-NST.

Mixed pleomorphic lobular and apocrine carcinoma of the breast: A case report suggesting pathogenesis.

Pleomorphic lobular carcinoma (PLC) of the breast is a variant of lobular carcinoma, characterized by loss of E-cadherin expression and high-grade morphologies. Whether the pathogenesis of PLC is in the ductal or the lobular lineage has been discussed. In this report, a case of PLC combined with apocrine carcinoma is presented. Histologically, the tumor showed two distinct carcinoma components: one was a typical apocrine carcinoma, and the other was a pleomorphic invasive lobular carcinoma. The former showed complete membranous expression of E-cadherin, whereas the latter aberrantly expressed it not on the cell membrane, but in the cytoplasm. Both components were triple-negative and strongly positive for GCDFP-15, suggesting apocrine differentiation. The intraductal component showed only a feature of apocrine ductal carcinoma in situ. This case suggests that apocrine carcinoma could be an origin of PLC.

T2-hypointense rim of breast mass lesions on magnetic resonance images: Radiologic-pathologic correlation.

We investigated the radiologic-pathologic correlation of a strong hypointense rim on T2-weighted images (T2-hypo-rim) surrounding breast mass lesions and evaluated its clinical significance. We retrospectively reviewed 3503 consecutive breast magnetic resonance imaging (MRI) examinations. The T2-hypo-rim was defined as a border of strong hypointensity compared with the fat signal on fat-suppressed T2-weighted images. Detected lesions with T2-hypo-rim were classified as a solid or cystic mass with MRI and correlated with histopathologic findings. Sixty-two masses (2%; 34 solid, 28 cystic) with T2-hypo-rim were detected [44 breast cancers, 18 benign lesions, including 15 (24%) papillary tumors]. Patients with cancer were significantly older than those with benign lesions (P = .002). Breast cancers were significantly larger than benign masses (P = .023). In 49 of 62 lesions (24 solid and 16 cystic cancers; three solid and six cystic benign masses), the rims were accurately correlated with the histopathologic findings. All malignant and benign cystic masses exhibited hemosiderin deposits in the cyst walls. However, 22 of 24 solid cancers and no solid benign masses exhibited hemosiderin at the tumor periphery (92% and 0%, respectively, P < .001). In addition, a thick fibrous capsule was present in nine (38%) of 24 solid cancers and none of the solid benign lesions. Strong T2-hypo-rims mostly correlated with hemosiderin deposits and/or sometimes fibrous capsules. Although the rims could not distinguish malignant from benign cystic lesions, they indicated malignancy in solid mass lesions on MRI. Additionally, the rims often indicated papillary tumors.

Kawasaki disease: Epidemiological differences between past and recent periods, and implications of distribution dynamism.

BACKGROUND: Epidemiological findings suggest that Kawasaki disease (KD) is mediated by infection, which triggers its onset. Although the mechanism of onset seems to involve preconditioning factors and triggering factors, the details remain unclarified. METHODS: Data for 330 662 patients reported in KD nationwide surveys in Japan implemented between 1961 and 2014 were chronologically compared in terms of patient age distribution, estimated mean onset age, and male-to-female ratio during four periods: pre-epidemic (P1), epidemic (P2), stable (P3), and recent (P4): 1961-1978, 1979-1986, 1987-1997, and 1998-2014, respectively. RESULTS: During P2, the number of patients aged 6 months-2 years increased, and the mean onset age was younger; during P4, however, the number of patients aged ≤1 year decreased, but the number of patients ≥2 years increased, with a flat onset age distribution chart, and the mean onset age was older. During P2, increases in the number of patients were accompanied by younger mean onset age, whereas during P4, increases in the number of patients were conversely accompanied by older mean onset ages. The male: female ratio tended to decrease during P2, but this tendency was not seen in P4. No outbreak occurred during a recent 28 year period (P3, P4). Specific preconditioning factors might have been present during the 8 years (P2) of the past three outbreaks. CONCLUSION: P2 and P4 were significantly different in epidemiological features. It is likely that they do not share the same mechanism of onset (preconditioning and/or trigger factors).

Comparison of visibility of circumscribed masses on Digital Breast Tomosynthesis (DBT) and 2D mammography: are circumscribed masses better visualized and assured of being benign on DBT?

OBJECTIVE: To compare the visibility of circumscribed masses on digital breast tomosynthesis (DBT) images and 2D mammograms and determine the usefulness of DBT for differentiation between benign and malignant circumscribed masses. METHODS: Seventy-one (19 malignant and 52 benign) mammographic well-circumscribed masses were included. Visibility of the masses and halo signs on DBT images were retrospectively compared with 2D mammograms. The effects of mammographic breast density on mass visibility were also evaluated. RESULTS: For DBT, 83% were superior and 17% were equivalent in visibility of the masses to that of 2D, and superiority of DBT was significantly enhanced in the high breast density group compared with the low breast density group (91% vs 68%, respectively, p = 0.016). Three lesions were only detected on DBT. There was no significant difference in the superiority of DBT for lesion visibility between malignant and benign masses. The halo sign was detected in 58% lesions on DBT and in 4% on 2D (p < 0.001). CONCLUSION: Circumscribed masses were better visualized on DBT than on 2D mammograms, particularly in high-density breasts. The halo sign often appeared on DBT and gave a clearer mass margin. However, circumscribed masses on DBT are not assured of being benign. KEY POINTS: • Circumscribed masses were better visualized on breast tomosynthesis than on 2D mammography. • Tomosynthesis visualized circumscribed masses better than 2D for all breast density categories. • Halo signs often appeared on tomosynthesis and contributed to detect circumscribed margins. • Circumscribed masses on tomosynthesis images are not assured of being benign lesions.

Real-time virtual sonography examination and biopsy for suspicious breast lesions identified on MRI alone.

OBJECTIVES: The purpose of our study was to assess whether there is a potential additional value of real-time virtual sonography (RVS) to second-look ultrasound (US) examination and biopsy for breast lesions identified on MRI alone. METHODS: A retrospective review of the records of 70 consecutive patients (78 lesions) with breast abnormalities identified on MRI alone was performed. All suspicious enhancing lesions were subsequently evaluated with second-look US. Lesions not observed on second-look US underwent RVS. Pathological findings were confirmed by subsequent percutaneous biopsy or excision. RESULTS: Of the 78 MRI-detected lesions, second-look US correlation was made in 50 (64 %), including 22 malignant and 28 benign lesions. The remaining 28 lesions (36 %) were scheduled to undergo RVS. Four lesions were not visible on the second breast MRI. The remaining 24 lesions were RVS correlated and underwent RVS-guided biopsy; these included seven malignant and 17 benign lesions. Overall, 74 of 74 (100 %) true MRI-detected lesions were confirmed by histological results without using MRI-guided breast biopsy. The cancer rate was 29 %. CONCLUSIONS: RVS can increase the sonographic detection and biopsy rate of lesions identified on breast MRI alone. KEY POINTS: • All 74 MRI-detected lesions were confirmed without using MRI-guided biopsy. • Four lesions were not visible on second breast MRI. • RVS can increase sonographic detection of lesions identified on breast MRI alone. • RVS-guided breast biopsy can be an alternative to MRI-guided biopsy.

Efficacy of a 3-month lifestyle intervention program using a Japanese-style healthy plate on body weight in overweight and obese diabetic Japanese subjects: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: The portion size of food is a determinant of energy intake, linking with obese traits. A healthy plate for portion control has recently been made in a Japanese style. The aim of the current study was to assess the efficacy of a lifestyle intervention program using the Japanese-style healthy plate on weight reduction in overweight and obese diabetic Japanese subjects. METHODS: We randomized overweight and obese diabetic subjects (n = 19, 10 women) into an intervention group including educational classes on lifestyle modification incorporating the healthy plate (n = 10) or a waiting-list control group (n = 9). The intervention period was three months, and the educational classes using the healthy plate were conducted monthly in a group session for the intervention group. The body weight, blood glycemic and metabolic measures, and psychosocial variables were measured at the baseline and after the 3-month intervention in both groups. The impression of the intervention was interviewed using a structured questionnaire. RESULTS: There was one drop-out in the control group. No adverse events were reported in the groups. Subjects in the intervention group had a greater weight change from baseline to the end of the 3-month intervention period (-3.7 +/- 2.5 [SD] kg in the intervention group vs. -0.1 +/- 1.4 kg in the control group, P = 0.002). Most subjects recorded that the use of a healthy plate could be recommended to other people. CONCLUSIONS: The lifestyle intervention program using the Japanese-style healthy plate, which was developed for portion control, may effectively reduce body weight in overweight and obese diabetic subjects in Japan. Further studies are needed to establish the efficacy of this methodology on weight management.

Non-contrast-enhanced breast MRI for evaluation of tumor volume change after neoadjuvant chemotherapy.

PURPOSE: Three-dimensional contrast-enhanced magnetic resonance imaging (3D-Ce-MRI) is a most powerful tool for evaluation of neoadjuvant chemotherapy (NAC). However, the use of contrast agent is invasive, expensive, and time consuming, Thus, contrast agent-free imaging is preferable. We aimed to investigate the tumor volume change after NAC using maximum intensity projection diffusion-weighted image (MIP-DWI) and 3D-Ce-MRI. METHOD: We finally enrolled 55 breast cancer patients who underwent NAC in 2018. All MRI analyses were performed using SYNAPSE VINCENT® medical imaging system (Fujifilm Medical, Tokyo, Japan). We evaluated the tumor volumes before, during, and after NAC. Tumor volume before NAC on 3D-Ce-MRI was termed Pre-CE and those during and after NAC were termed Post-CE. The observer raised the lower end of the window width until the tumor was clearly visible and then manually deleted the non-tumor tissues. A month thereafter, the same observer who was blinded to the 3D-Ce-MRI results randomly evaluated the tumor volumes (Pre-DWI and Post-DWI) using MIP-DWI with the same method. Tumor volume change between ΔCE (Pre-CE - Post-CE/Pre-CE) and ΔDWI (Pre-DWI - Post-DWI/Pre-DWI) and the processing time for both methods (Time-DWI and Time-CE) were compared. RESULTS: We enrolled 55 patients. Spearman's rho between ΔDWI and ΔCE for pure mass lesions, and non-mass enhancement (NME) was 0.89 (p < 0.01), 0.63(p < 0.01) respectively. Time-DWI was significantly shorter than Time-CE (41.3 ± 21.2 and 199.5 ± 98.3 respectively, p < 0.01). CONCLUSIONS: Non-contrast-enhanced Breast MRI enables appropriate and faster evaluation of tumor volume change after NAC than 3D-Ce-MRI especially for mass lesions.

Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1), a nationwide cluster randomized trial of type 2 diabetes prevention by telephone-delivered lifestyle support for high-risk subjects detected at health checkups: rationale, design, and recruitment.

BACKGROUND: Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes (T2DM). To contain the growing population of T2DM, it is critical to clarify effective and efficient settings for intervention and modalities for intervention delivery with a wide population reach.The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) is a cluster randomized controlled trial to test whether goal-focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting. This paper describes the study design and recruitment of the study subjects. METHODS: For the recruitment of study subjects and their follow-up annually over 3 years, we employed health checkups conducted annually at communities and worksites. Health care divisions recruited from communities and companies across Japan formed groups as a cluster randomization unit. Candidates for the study, aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/l, were recruited from each group using health checkups results in 2006. Goal-focused lifestyle support is delivered by healthcare providers via telephone over a one-year period. Study subjects will be followed-up for three years by annual health checkups. Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report, which is confirmed by referring to medical cards. RESULTS: Forty-three groups (clusters), formed from 17 health care divisions, were randomly assigned to an intervention arm (22 groups) or control arm (21 clusters) between March 2007 and February 2008. A total of 2840 participants, 1336 from the intervention and 1504 from the control arm, were recruited. Consent rate was about 20%, with no difference between the intervention and control arms. There were no differences in cluster size and characteristics of cluster between the groups. There were no differences in individual characteristics between the study arms. CONCLUSION: We have launched J-DOIT1, a nation-wide trial to prevent the development of T2DM in high-risk individuals using telephone-delivered intervention. This trial is expected to contribute to evidence-based real-world preventive practices. TRIAL REGISTRATION: UMIN000000662.

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: risk factors of IBTR and validation of the MD Anderson Prognostic Index.

BACKGROUND: There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast-conserving surgery plus radiotherapy (breast-conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors. METHODS: The authors collected data from 375 patients who underwent BCT and received NAC and analyzed the risk of IBTR associated with undergoing BCT after NAC. The usefulness of the MD Anderson Prognostic Index (MDAPI) for IBTR also was validated using the current data set. RESULTS: The median follow-up was 47.8 months, and the 4-year IBTR-free survival rate was 95.6%. Multivariate analysis demonstrated that estrogen receptor (ER) status and multifocality of the residual tumor were associated significantly with IBTR-free survival. In addition, patients who had ER-positive and human epidermal growth factor 2 (HER2)-negative tumors did not develop IBTR during the observation period. Although prognostic stratification according to MDAPI was relatively good for the prediction of IBTR in the study patients, the IBTR rate in the high-risk group was not very high and was lower than that in the intermediate-risk group. Multivariate analyses demonstrated that IBTR was an independent predictive factor for overall survival. CONCLUSIONS: ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER-positive and HER2-negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor.

Is bilirubin/albumin ratio correlated with unbound bilirubin concentration?

BACKGROUND: The American Academy of Pediatrics guidelines recommend that the total bilirubin (TB)/albumin (Alb) ratio (B/A ratio), instead of serum concentration of unbound bilirubin (UB), can be used with TB for determining treatment modality for jaundiced newborns ≥ 35 weeks of gestation. It is unknown, however, whether the B/A ratio is actually correlated with serum UB. METHODS: Four hundred and ninety-seven serum samples were obtained from 209 newborns ≥ 35 weeks of gestation, who were admitted to Kobe University Hospital. Serum UB concentration was measured using the glucose oxidase-peroxidase method. Serum TB and Alb concentrations were measured on spectrophotometry. B/A ratios were calculated and were linearly compared with serum UB. Furthermore, the accuracy of the B/A ratio was evaluated. RESULTS: The B/A ratio was significantly correlated with serum UB concentration. A serum UB concentration of 0.6 µg/dL was in agreement with a B/A ratio of 0.5. For comparison of the number of newborns who had serum UB concentrations ≥ or <0.6 µg/dL and B/A ratios ≥ or <0.5, we found the following characteristics: the concordance rate between serum UB concentrations and the B/A ratio was 94%, sensitivity was 51%, and specificity was 99%. CONCLUSIONS: The B/A ratio is significantly correlated with serum UB concentration in newborns ≥ 35 weeks of gestation. The B/A ratio, however, is underestimated when serum UB concentrations are >0.6 µg/dL.

'Care-ful' boundary negotiation: Curating translocal subjectivities among Japanese women in London.

This paper explores the everyday experience of Japanese female migrants in London. Asking how culture can offer us a lens through which to understand the diversity and heterogeneity of care in this globalised world, the Japanese concept of omoiyari, as curation of landscapes of care, is used as an analytical lens to unpack the interplay between culture, care and identity, illuminating the boundary-drawing aspects of ethics of care with which people make ongoing distinctions between self and others, and constructing translocal subjectivities. Understanding care as a form of communication, this paper uncovers the contextual and relational formation of care and self, and how this is enabled as well as constrained by culture. It contributes to an understanding of the relational formation of care in which caring practice is neither static nor embedded in place and culture, but is rather shaped through relationships dynamically, while social relationships in turn also shape the meaning of care.

Comprehensive miRNA and DNA Microarray Analyses Reveal the Response of Hepatic miR-203 and Its Target Gene to Protein Malnutrition in Rats.

Adequate protein nutrition is essential for good health. Effects of protein malnutrition in animals have been widely studied at the mRNA level with the development of DNA microarray technology. Although microRNAs (miRNAs) have attracted attention for their function in regulating gene expression and have been studied in several disciplines, fewer studies have clarified the effects of protein malnutrition on miRNA alterations. The present study aimed to elucidate the relationship between protein malnutrition and miRNAs. Six-week old Wistar male rats were fed a control diet (20% casein) or a low-protein diet (5% casein) for two weeks, and their livers were subjected to both DNA microarray and miRNA array analysis. miR-203 was downregulated and its putative target Hadhb (hydroxyacyl-CoA dehydrogenase ß subunit), known to regulate ß-oxidation of fatty acids, was upregulated by the low-protein diet. In an in vitro experiment, miR-203 or its inhibitor were transfected in HepG2 cells, and the pattern of Hadhb expression was opposite to that of miR-203 expression. In addition, to clarifying the hepatic miRNA profile in response to protein malnutrition, these results showed that a low-protein diet increased Hadhb expression through downregulation of miR-203 and induced ß-oxidation of fatty acids.

Can breast MRI and adjunctive Doppler ultrasound improve the accuracy of predicting pathological complete response after neoadjuvant chemotherapy?

BACKGROUND: To examine the accuracy of MRI and Doppler ultrasound (US) for detecting residual tumor after neoadjuvant chemotherapy (NAC) for breast cancer and evaluate whether adjunctive Doppler US improves the MRI accuracy. METHODS: We reviewed 276 invasive breast cancer cases treated with NAC. Tumors were classified into four subtypes based on estrogen receptor and HER2 status. Response to NAC was evaluated using contrast-enhanced MRI and Doppler US. Residual Doppler flow was assumed to indicate a residual tumor. MRI and Doppler findings were compared with the histopathological findings of resected specimens. Pathological complete response (pCR) was defined as neither in situ nor invasive cancer left. RESULTS: Of the 276 tumors, imaging complete responses were observed using MRI and Doppler US in 62 (22%) and 111 (40%), respectively, whereas pCR was achieved in 44 (16%). MRI and Doppler US predicted residual tumor with 88% and 69% sensitivity, 80% and 91% specificity, 87% and 73% accuracy, 96% and 98% PPV, and 56% and 36% NPV, respectively. The accuracies of MRI and Doppler US were significantly higher for HER2-negative than HER2-positive tumors (p < 0.001 and p = 0.043, respectively). Seven (26%) of 27 false-negative cases identified by MRI were correctly diagnosed as positives with adjunctive Doppler US. CONCLUSIONS: Although MRI accurately detected residual tumor with 87% accuracy, this was still not sufficient to meet clinical demands and differed with tumor subtype. Adjunctive Doppler US in cases that appear to show a complete response on MRI might reduce chances of false negatives and increase the NPV of MRI for predicting residual tumor.

Study on the Causes, Types, and Mechanisms of Childhood Injuries-Age and Disease Specificity.

INTRODUCTION: To clarify the causes, types, and mechanisms of injuries in children, we collected injury cases and analyzed their causes. METHODS: During the 3-year period from 2013, we collected injury cases from three sources: nursery schools and kindergartens (A), emergency clinics of hospitals (B), and schools and a clinic for the developmentally disabled (C), using a format designed by Safe Kids Japan. RESULTS: In all, 383 cases were collected during the 3-year period. The causes of the injuries in group A were crashes, falls, and so on. The types of injuries were cuts, bruises, fractures, injuries of teeth, etc. Dislocations and abrasions were prominent in nursery school children (aged less than 3 years) and bone fractures were prominent in kindergarten children aged more than 3 years.Group B consisted of 144 cases. The most common causes of injuries were falls, traffic accidents, and so on, and the types of injuries were fractures, abrasions, sprains, etc. The incidence of fractures was particularly high and 50% of the accidents were bicycle accidents.Group C consisted of 41 cases. Although the age distribution was similar to that of group B, the types of accidents and injuries were similar to those of group A.The Bodygraphic Injury Surveillance System (BISS) analysis showed that groups A and C were similar, that is, injuries occurred mainly to the head, whereas in group B, the extremities were mainly affected. CONCLUSIONS: We analyzed the causes, types, and mechanisms of childhood injuries. The BISS may help to clarify the mechanisms of injuries in childhood.

Impact of telephone support programme using telemonitoring on stage of change towards healthy eating and active exercise in people with prediabetes.

INTRODUCTION: This study evaluated the impact of a telephone support programme with telemonitoring on changes in healthy eating and active exercise in adults with prediabetes using the stage of change framework. METHODS: We performed a post hoc analysis using data from the Japan Diabetes Outcome Trial-1. A total of 2607 participants aged 20-65 years with impaired fasting glucose were recruited from the workplace/community in Japan and randomized to a one year telephone support programme intervention arm (n = 1240) or self-directed control arm (n = 1367). Participants in both arms received monthly data feedback from a weight scale and pedometer. The main outcome measure was the stages of change toward healthy eating and active exercise. The secondary outcome was fasting plasma glucose (FPG). RESULTS: After the one year intervention, the adjusted odds ratio of progressing to the action/maintenance stage in the intervention vs. control arm for healthy eating was 1.31 (95% confidence interval (CI) 1.21-1.43; p < 0.001), but that for active exercise was 1.07 (95% CI 0.99-1.15; p = 0.062). The intervention decreased FPG levels in participants in the contemplation stage, but not in the precontemplation, preparation and action/maintenance stages. DISCUSSION: These findings suggest that the telephone support programme by healthcare providers advanced the stage of changes toward healthy eating in people with prediabetes. In particular, it decreased FPG levels in the contemplation stage.

Identification of tumor microenvironment-associated immunological genes as potent prognostic markers in the cancer genome analysis project HOPE.

Project High-tech Omics-based Patient Evaluation (HOPE), which used whole-exome sequencing and gene expression profiling, was launched in 2014. A total of ~2,000 patients were enrolled until March 2016, and the survival time was observed up to July 2019. In our previous study, a tumor microenvironment immune type classification based on the expression levels of the programmed death-ligand 1 (PD-L1) and CD8B genes was performed based on four types: A, adaptive immune resistance; B, intrinsic induction; C, immunological ignorance; and D, tolerance. Type A (PD-L1+ and CD8B+) exhibited upregulated features of T helper 1 antitumor responses. In the present study, survival time analysis at 5 years revealed that patients in type A had a better prognosis than those in other categories [5 year survival rate (%); A (80.5) vs. B (73.9), C (73.4) and D (72.6), P=0.0005]. Based on the expression data of 293 immune response-associated genes, 62 specific genes were upregulated in the type A group. Among these genes, 18 specific genes, such as activated effector T-cell markers (CD8/CD40LG/GZMB), effector memory T-cell markers (PD-1/CD27/ICOS), chemokine markers (CXCL9/CXCL10) and activated dendritic cell markers (CD80/CD274/SLAMF1), were significantly associated with a good prognosis using overall survival time analysis. Finally, multivariate Cox proportional hazard regression analyses of overall survival demonstrated that four genes (GZMB, HAVCR2, CXCL9 and CD40LG) were independent prognostic markers, and GZMB, CXCL9 and CD40LG may contribute to the survival benefit of patients in the immune type A group.