Remarkable remission of symptomatic dermatomyositis after curative breast cancer surgery.

Dermatomyositis (DM) is an autoimmune disease that causes proximal muscle weakness in the extremities leading to severe immobility and dysphagia. Approximately 20% of patients with DM are positive for anti-TIF-1γ antibody and frequently accompanied by malignant tumors. Although DM remission after tumor resection has been reported, the indications for surgery in patients with severe DM are unknown. Herein, we report a case of a 79-year-old Japanese woman who presented with breast cancer and anti-TIF-1γ antibody-positive DM. She became bedridden shortly after DM onset. Although pulsed steroid therapy, intravenous immunoglobulin, tacrolimus, and endocrine therapy with fulvestrant did not improve her symptoms, tumor resection with axillary lymph node dissection resulted in complete remission of the DM after 8 months. Immunohistochemistry revealed high expression of TIF-1γ in cancer cells, both in the primary tumor and axillary lymph nodes. Since the serum levels of anti-TIF-1γ antibody decreased after the surgery, the existence of breast cancer with TIF-1γ expression may have contributed to the worsening of DM. The present case suggests that curative surgery should be considered as a treatment option even if the patient has severe symptoms, such as immobility and dysphagia. Careful discussions with patients and multidisciplinary collaboration are essential to make surgery feasible, particularly for those with severe symptomatic DM.

Anthracycline-based hepatic arterial infusion chemotherapy achieved 17 months of disease regression in a patient with breast cancer liver metastases resistant to multiple systemic chemotherapies.

Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive LMs who cannot tolerate systemic therapy has been reported. Herein, we report a case of breast cancer LMs that were controlled by anthracycline-based HAIC. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38 months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21 months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40 mg/body epirubicin on day 1, 4 mg/body mitomycin C on days 1 and 15, and 500 mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses). In response to HAIC, the LMs remarkably regressed and were controlled for 17 months without severe adverse effects. HAIC was stopped when multiple brain metastases arose, and the patient died 2 months later. This case suggests that HAIC is a reasonable option for patients with extensive LMs, even in the late stage of treatment. HAIC recipients should be carefully selected through multidisciplinary discussions as the survival benefits of HAIC over systemic treatment remain unclear. Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.

Quantitative analysis of the effect of docetaxel-induced edema on quality of life in patients with breast cancer and related factors: a prospective cohort study.

BACKGROUND: Systemic edema is an adverse effect of docetaxel chemotherapy and causes distress to patients, including those receiving this agent for breast cancer. However, its characteristics and factors related to its effect on quality of life (QoL) have not been adequately investigated. In this study, we assessed systemic edema quantitatively, explored related factors, and evaluated QoL in patients receiving docetaxel for breast cancer. METHODS: The study had a prospective cohort design and included 37 patients with no known history of swelling who were treated with docetaxel between September 2019 and April 2022. Patients were examined at the start, middle, and end of their course of treatment and 1 and 2 months later. Body water content, body mass, fat mass, and muscle mass were quantified using bioelectrical impedance analysis. Systemic edema was evaluated with reference to the Common Terminology Criteria for Adverse Events. The timing of development of systemic edema at any anatomical site that was grade 2 or worse was recorded. QoL was assessed using the Quality of Life-Anti Cancer Drug scale. Nutrition was evaluated using the Brief-type self-administered diet history questionnaire. Multivariable logistic regression analysis was performed to identify related factors. QoL was also compared between patients with edema and those without edema. RESULTS: Systemic edema developed in 67% of the study participants and was most prevalent at the end of treatment. Body fat mass (adjusted odds ratio [aOR] 0.802, 95% confidence interval [CI] 0.651-0.988, p = 0.038), disease stage (aOR 3.279, 95% CI 0.493-21.793, p = 0.219), and history of alcohol consumption (aOR 0.141, 95% CI 0.013-1.521, p = 0.106) were identified as risk factors for docetaxel-induced edema. Participants who developed systemic edema experienced more physical, vital, and emotional distress 1 month after treatment than those who did not. There was no association between systemic edema and nutrition. CONCLUSIONS: Systemic edema may develop after treatment with docetaxel and increase distress in patients with a high body fat mass. Patients at risk of systemic edema should be informed in advance about the potential frequency, location, and timing of its onset and encouraged to self-manage this condition.

Overall survival in Japanese patients with ER+/HER2- advanced breast cancer treated with first-line palbociclib plus letrozole.

BACKGROUND: An open-label, single-arm, Japanese phase 2 study (J-Ph2) investigated the efficacy and safety of first-line (1L) palbociclib (PAL) + letrozole (LET) in postmenopausal Japanese women with ER+/HER2- advanced breast cancer (ABC). In the final analysis, median progression-free survival was 35.7 months (95% CI 21.7-46.7); but overall survival (OS) data were immature. Here, we report the findings from a follow-up study of J-Ph2 (NCT04735367) evaluating OS and subsequent therapy in these Japanese women. METHODS: Patients (N = 42) who participated in J-Ph2 were enrolled in the OS follow-up study. The primary endpoint was OS and secondary endpoints included type and duration of subsequent therapy. RESULTS: Patients were a median age of 62.5 years; 48% had visceral metastases. At a median follow-up of 89.7 months, the median OS was 85.4 months (95% CI 64.3-not estimable). Median OS was longer in patients with nonvisceral versus visceral metastases (not reached vs 67.3 months), or with treatment-free interval > 12 months versus ≤ 12 months (85.4 vs 45.4 months), or with treatment duration ≥ 24 months versus < 24 months (not reached vs 47.5 months). Of patients who received a first subsequent therapy (81%), most (67%) continued endocrine-based therapy, while 7% received chemotherapy. The median duration of the first subsequent therapy was 8.3 months (95% CI 3.9-12.2), and the median chemotherapy-free survival was 69.1 months (95% CI 24.2-85.4). CONCLUSIONS: In this population of Japanese women with ER+/HER2- ABC, median OS was over 7 years with 1L PAL + LET, supporting the use of 1L PAL + endocrine therapy. TRIAL NUMBER: NCT04735367.

Comparison of cisplatin-based versus standard preoperative chemotherapy in patients with operable triple-negative breast cancer: propensity score matching and inverse probability of treatment weighting analysis.

PURPOSE: The efficacy of carboplatin is non-equivalent to that of cisplatin (CDDP) for various tumor types in curative settings. However, the role of CDDP in operable triple-negative breast cancer (TNBC) patients remains unknown. We conducted a multicenter observational study to examine the effects of CDDP added to preoperative chemotherapy in patients with TNBC. METHODS: This retrospective study consecutively included previously untreated patients with stage I-III TNBC treated with preoperative chemotherapy with or without CDDP. The primary endpoint was distant disease-free survival (DDFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding biases in comparisons between the two groups. RESULTS: A total of 138 patients were enrolled in the study. Of these, 52 were in the CDDP group and 86 in the non-CDDP group. DDFS was significantly better in the CDDP group than in the non-CDDP group (unadjusted hazard ratio (HR) 0.127 and p < 0.001, PSM HR 0.141 and p < 0.003, IPTW HR 0.123 and p = < 0.001). Furthermore, among the patients with residual cancer burden (RCB) class II/III, DDFS was better in the CDDP group than in the non-CDDP group (unadjusted HR 0.192 and p = 0.013, PSM HR 0.237 and p = 0.051, IPTW HR 0.124 and p = 0.059). CONCLUSION: Our study showed that CDDP-containing regimens achieved favorable prognoses in patients with operable TNBC, especially for the RCB class II/III population. Confirmative studies are warranted to elucidate the role of CDDP in TNBC treatment.

Discovery of lipid profiles in plasma-derived extracellular vesicles as biomarkers for breast cancer diagnosis.

Lipids are a major component of extracellular vesicles; however, their significance in tumorigenesis and progression has not been well elucidated. As we previously found that lipid profiles drastically changed in breast tumors upon progression, we hypothesized that lipid profiles of plasma-derived extracellular vesicles could be utilized as breast cancer biomarkers. Here, we adopted modified sucrose cushion ultracentrifugation to isolate plasma-derived extracellular vesicles from breast cancer (n = 105), benign (n = 11), and healthy individuals (n = 43) in two independent cohorts (n = 126 and n = 33) and conducted targeted lipidomic analysis. We established a breast cancer diagnostic model comprising three lipids that showed favorable performance with the area under the receiver operating characteristic curve of 0.759, 0.743, and 0.804 in the training, internal validation, and external test sets, respectively. Moreover, we identified several lipids that could effectively discriminate breast cancer progression and subtypes: phosphatidylethanolamines and phosphatidylserines were relatively higher in Stage III, whereas phosphatidylcholines and sphingomyelins were higher in Stage IV; phosphatidylcholines and ceramides were correspondingly concentrated in HER2-positive patients, while lysophosphatidylcholines and polyunsaturated triglycerides were concentrated in the triple-negative breast cancer subtype. Lipid profiling of plasma-derived extracellular vesicles is a non-invasive and promising approach for diagnosing, staging, and subtyping breast cancer.

Evolutionary histories of breast cancer and related clones.

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1-3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient's early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.

A 65-Year-Old Man With Massive Hemoptysis.

CASE PRESENTATION: A 65-year-old man experienced a cough and mild hemoptysis suddenly one morning. He was prescribed tranexamic acid and carbazochrome salicylate by the local clinic at the first visit, and his hemoptysis stopped. However, 2 days later, he experienced recurrent hemoptysis that was prolonged intermittently. He had slight dyspnea and chest discomfort, but no other symptoms, such as sputum, fever, or chest pain. He was referred to our hospital for further assessment of hemoptysis. He had experienced mild hemoptysis of unknown causes 8 years earlier without recurrence until this episode. He had bronchial asthma that was treated with an inhaled corticosteroid and hypertension and hyperuricemia that were untreated with medication. He had no known allergies or family history of lung disease. He did not smoke. The patient denied alcohol consumption, any recent travel, or exposure to TB.

Feasibility of Dedicated Breast Positron Emission Tomography Image Denoising Using a Residual Neural Network.

Objectives: This study aimed to create a deep learning (DL)-based denoising model using a residual neural network (Res-Net) trained to reduce noise in ring-type dedicated breast positron emission tomography (dbPET) images acquired in about half the emission time, and to evaluate the feasibility and the effectiveness of the model in terms of its noise reduction performance and preservation of quantitative values compared to conventional post-image filtering techniques. Methods: Low-count (LC) and full-count (FC) PET images with acquisition durations of 3 and 7 minutes, respectively, were reconstructed. A Res-Net was trained to create a noise reduction model using fifteen patients' data. The inputs to the network were LC images and its outputs were denoised PET (LC + DL) images, which should resemble FC images. To evaluate the LC + DL images, Gaussian and non-local mean (NLM) filters were applied to the LC images (LC + Gaussian and LC + NLM, respectively). To create reference images, a Gaussian filter was applied to the FC images (FC + Gaussian). The usefulness of our denoising model was objectively and visually evaluated using test data set of thirteen patients. The coefficient of variation (CV) of background fibroglandular tissue or fat tissue were measured to evaluate the performance of the noise reduction. The SUVmax and SUVpeak of lesions were also measured. The agreement of the SUV measurements was evaluated by Bland-Altman plots. Results: The CV of background fibroglandular tissue in the LC + DL images was significantly lower (9.10±2.76) than the CVs in the LC (13.60± 3.66) and LC + Gaussian images (11.51± 3.56). No significant difference was observed in both SUVmax and SUVpeak of lesions between LC + DL and reference images. For the visual assessment, the smoothness rating for the LC + DL images was significantly better than that for the other images except for the reference images. Conclusion: Our model reduced the noise in dbPET images acquired in about half the emission time while preserving quantitative values of lesions. This study demonstrates that machine learning is feasible and potentially performs better than conventional post-image filtering in dbPET denoising.

Diagnostic Utility of a Mycobacterium Multiplex PCR Detection Panel for Tuberculosis and Nontuberculous Mycobacterial Infections.

The prevalence of nontuberculous mycobacterial diseases is increasing worldwide, and tuberculosis remains highly prevalent. Rapid and accurate microbial diagnoses of both tuberculosis and nontuberculous mycobacterial infections are required. A novel PCR-reverse sequence-specific oligonucleotide probe (PCR-rSSO) method-based mycobacterial detection panel (Myco-Panel) test was developed for the rapid identification of 30 mycobacterial species and subspecies. Clinical respiratory samples were collected from patients with suspected or confirmed tuberculosis and nontuberculous mycobacterial lung disease and those with other respiratory diseases. Myco-Panel tests were performed on the samples, and liquid mycobacterial culture and identification were performed for reference according to housekeeping gene sequences of mycobacteria in positive culture tubes. Furthermore, to assess the detection performance for several mycobacterial species rarely recovered in Japan, the accuracy of the Myco-Panel test was investigated using stock mycobacterial type strains and clinical isolates. A total of 178 clinical respiratory samples were analyzed. The Myco-Panel and sequence-based identification results for mycobacterial cultures were 83.1% concordant (kappa coefficient, 0.785 [95% confidence interval, 0.716 to 0.854]). The Myco-Panel correctly identified 281 of the 283 type strains and clinical isolates tested. The Myco-Panel test could accurately detect several mycobacterial species from clinical respiratory samples and mycobacterial suspensions. Rapid and accurate identification of pathogens using respiratory samples is possible using the Myco-Panel. IMPORTANCE Species identification is important for the diagnosis of mycobacterial infections and decisions on treatment regimens. The Myco-Panel test accurately detects clinically common mycobacterial species that cause respiratory infections from clinical respiratory samples and mycobacterial suspensions. The rapid identification of multiple mycobacterial species will provide clinically useful information for the management of patients. Although we understand that the current diagnostic criteria require mycobacterial culture results in general for the diagnosis of nontuberculous mycobacterial infection, mycobacterial culture examination is a time-consuming process. The detection of potentially causative agents directly from clinical samples will aid in practical diagnosis and decision-making for rapid treatment initiation. This is a new laboratory method for species identification, and evaluating its performance is important.

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2-mutation carriers.

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients.

Validity of Platelia Aspergillus IgG and Aspergillus Precipitin Test To Distinguish Pulmonary Aspergillosis from Colonization.

When Aspergillus, an ubiquitous, saprophytic fungus, is detected in respiratory tract specimens collected from chronic respiratory disease patients, it is important to determine whether it is a true infection or colonization. We investigated the usefulness of the Bio-Rad Platelia Aspergillus IgG (Platelia Aspergillus IgG) enzyme-linked immunosorbent assay (ELISA) method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Between January 2017 and November 2021, 51 confirmed, untreated pulmonary aspergillosis (33 chronic pulmonary aspergillosis [CPA] and 18 allergic bronchopulmonary aspergillosis [ABPA]) and 77 colonization patients were included in this study. At first, the conventional cutoff value was utilized in assessing the validity of the two antibody tests for distinguishing pulmonary aspergillosis from colonization. The Platelia Aspergillus IgG cutoff value was then reevaluated to fit this situation. Finally, differences in test accuracy dependent on Aspergillus species were assessed for both antibody tests by comparing cases with Aspergillus fumigatus complex and those with non-fumigatus Aspergillus complex. Both antibody tests demonstrated significantly higher positive rates for pulmonary aspergillosis (P < 0.0001) than colonization. The cutoff value should be 15.7 arbitrary units (AU)/mL to best distinguish infection from colonization, which was higher than the conventional value of 10 AU/mL. The diagnostic sensitivity of Platelia Aspergillus IgG for the non-fumigatus Aspergillus complex was inferior to the A. fumigatus complex (P = 0.019). In conclusion, both Aspergillus antibody tests were valid to distinguish infection from colonization, although we should note the higher cutoff value for Platelia Aspergillus IgG and the lower sensitivity in cases of non-fumigatus Aspergillus infection. IMPORTANCE Pulmonary aspergillosis is the most common pulmonary fungal infection. However, Aspergillus is a ubiquitous, saprophytic fungus; it can be detected in respiratory specimens even in the absence of infection. Especially since Aspergillus is detected in respiratory specimens collected from patients with chronic respiratory disease, it is important to determine whether it is true infection or colonization. We investigated the validity of the Platelia Aspergillus IgG ELISA method and the Aspergillus precipitin test to distinguish pulmonary aspergillosis from colonization. Both antibody tests were considered useful in differentiating true infection from colonization in respiratory practice. The appropriate cutoff value for Platelia Aspergillus IgG was higher than the conventional value, and it was also noted that the sensitivity of both antibody tests for non-fumigatus Aspergillus complex was low. This study will be significant in real-world clinical practice of pulmonary aspergillosis using antibody tests in respiratory care.

The Treatment and Prognosis of Older Tuberculosis Patients with a Poor Performance Status Caused by Underlying Diseases.

Objective The incidence of tuberculosis in Japan has been decreasing in the overall population but is increasing in older patients ≥90 years old. A poor performance status due to underlying diseases makes it difficult for patients with tuberculosis to receive standard oral treatment. However, there is no consensus concerning alternative treatments. This study examined the treatments and outcomes of older patients with tuberculosis and a poor performance status and determined the limitations of tuberculosis treatment for them. Methods We retrospectively enrolled 121 older patients with tuberculosis and a performance status of 3 or 4 due to underlying diseases during their hospitalization between April 2015 and March 2017 at National Hospital Organization Tokyo National Hospital. We classified them according to the drug administration route (oral, enteral, and injection routes) on admission and compared the characteristics and prognoses among the three groups. Results There were 79 patients in the oral route group, 28 (35.4%) of whom died during hospitalization. Among the 15 patients in the enteral route group, 6 (40.0%) died. Among the 27 patients in the injection route group who received non-oral agents, 22 (81.5%) died. The prognosis of the injection route group was poor, with a median survival time of 21 days. Conclusion Treatment success cannot be expected with injection treatment in patients with a poor general condition because of complications. Although injection treatment may be a viable alternative treatment, its establishment as the standard treatment cannot be currently endorsed.

Impact of lung cancer surgery on comorbid Mycobacterium avium complex lung disease-A case series.

The number of cases with Mycobacterium avium and Mycobacterium intracellulare lung diseases (Mycobacterium avium complex lung disease [MACLD]) are increasing globally. Lung cancer can sometimes present as a comorbidity with MACLD; however, the clinical presentation and outcomes of comorbid MACLD following lung cancer resection remain unclear. Therefore, we retrospectively assessed 17 patients with MACLD undergoing lung cancer resection to determine the impact of lung cancer surgery on comorbid MACLD. Of the 17 patients, Mycobacterium avium and Mycobacterium intracellulare were present in 15 and 2 patients, respectively; 14 patients had stage I lung cancer and underwent lobectomy. Ten patients were postoperatively observed for MACLD without any further intervention, five patients underwent additional resection for conspicuous MACLD lesions, and the remaining two patients underwent complete resection for MACLD and lung cancer within the same lobe followed by rifampicin, ethambutol, and clarithromycin (RECAM) therapy. Seven patients exhibited postoperative MACLD exacerbation, six of whom developed exacerbation in the operated ipsilateral residual lobes. Six of these seven patients received RECAM, three of whom (43%) subsequently exhibited improvement. Attention should be paid to MACLD exacerbation during postoperative follow-up, especially in ipsilateral lobes. Although RECAM therapy may be beneficial in alleviating MACLD exacerbation, further investigation is warranted to validate these results.

Indocyanine green-enhanced thoracoscopic localization of parasternal lymph node: How to do it.

Small, non-palpable, parasternal lymph nodes can be difficult to locate during minimally invasive thoracoscopy. We here present a simple technique for thoracoscopic localization of small parasternal lymph nodes using echo-guided injection of indocyanine green. This technique rapidly marks the whole chain of enhanced lymph nodes for radical resection, enabling accurate endoscopic resection of small parasternal lymph nodes.

Severe Asthma Where Eosinophilic Granulomatosis with Polyangiitis Became Apparent after the Discontinuation of Dupilumab.

The use of biologic agents has enabled control of severe asthma, but there is a risk that eosinophilic granulomatosis with polyangiitis (EGPA) may be masked in some cases. We herein report a 71-year-old man who was administered dupilumab for 2 years to stabilize his asthma symptoms. A few months after discontinuation of dupilumab administration, an increase in the eosinophil count in peripheral blood, leg pain, and a rash appeared. Based on pathology, he was diagnosed with EGPA. EGPA in this case was considered to have become apparent due to the discontinuation of dupilumab administration.

The accuracy and clinical impact of the morphological identification of Aspergillus species in the age of cryptic species: A single-centre study.

BACKGROUND: Aspergillus spp. is identified morphologically without antifungal susceptibility tests (ASTs) in most clinical laboratories. The aim of this study was to examine the clinical impact of the morphological identification of Aspergillus spp. to ensure the adequate clinical management of Aspergillus infections. PATIENTS/METHODS: Aspergillus isolates (n = 126) from distinct antifungal treatment-naïve patients with aspergillosis were first identified morphologically, followed by species-level identification via DNA sequencing. An AST for itraconazole (ITC) and voriconazole (VRC) was performed on each Aspergillus isolate. RESULTS: Based on the genetic test results, morphology-based identification was accurate for >95% of the isolates at the species sensu lato level although the test concordance of Aspergillus spp. with low detection rates was low. The rates of cryptic species were found to be 1.2% among the isolates of A. fumigatus complex and 96.8% in the A. niger complex. Cryptic species with lower susceptibilities to antifungal drugs than sensu stricto species among the same Aspergillus section were as follows: The A. lentulus (n = 1) isolates had low susceptibilities to azoles among the A. fumigatus complex species (n = 86), and A. tubingensis isolates (n = 18) exhibited lower susceptibility to azoles among the A. niger complex species (n = 31). CONCLUSION: Diagnostic accuracy was high at the A. fumigatus and A. niger complex level. However, in the presence of cryptic species, a solely morphological identification was insufficient. Particularly, ITC and VRC might be inappropriate for aspergillosis treatment when the A. niger complex is identified morphologically because it is possible that the Aspergillus isolate is A. tubingensis.

Non-fumigatus Aspergillus Infection Associated with a Negative Aspergillus Precipitin Test in Patients with Chronic Pulmonary Aspergillosis.

Aspergillus antibody testing is key for the clinical diagnosis of chronic pulmonary aspergillosis (CPA) with high sensitivity. However, false-negative results in patients with CPA might be obtained, depending on the Aspergillus species. The aim of this study was to investigate which factors are associated with false-negative results in Aspergillus precipitin tests and whether the sensitivity of precipitin tests in CPA is influenced by Aspergillus fumigatus and non-fumigatus Aspergillus species. Between February 2012 and December 2020, 116 consecutive antifungal treatment-naive patients with CPA were identified and included in this retrospective chart review. Aspergillus species isolated from the respiratory tract of patients were identified by DNA sequencing. Characteristics of patients with positive and negative results for Aspergillus precipitin tests were compared. The sensitivity of the Aspergillus precipitin tests was compared between patients with A. fumigatus-associated CPA and non-fumigatus Aspergillus-associated CPA. A non-fumigatus Aspergillus species was the only factor significantly associated with negative Aspergillus precipitin test results in patients with CPA in the multivariate analysis (hazard ratio, 8.3; 95% confidence interval, 3.2 to 22.1; P < 0.0001). The positivity of the Aspergillus precipitin test for patients with non-fumigatus Aspergillus-associated CPA was lower than that for patients with A. fumigatus-associated CPA (84.8% versus 37.9%; P < 0.0001). These results revealed that the presence of non-fumigatus Aspergillus-associated CPA should be considered with a negative Aspergillus precipitin test; this finding may prevent diagnostic delay or misdiagnosis for CPA.

Usefulness and Prospects of Sentinel Lymph Node Biopsy for Patients With Breast Cancer Using the Medical Imaging Projection System.

BACKGROUND: The Medical Imaging Projection System (MIPS) projects indocyanine green (ICG) fluorescence images directly on the surgical field using a projection mapping technique. We conducted an observational study of sentinel lymph node (SLN) biopsy using the prototype MIPS; we found a high identification rate. However, the number of SLN-positive cases was small, and the sensitivity could not be evaluated. The aim of this study was to investigate the clinical usefulness of the MIPS assisted ICG fluorescence method using commercially available equipment. METHODS: This was a retrospective observational study. Patients with primary breast cancer who underwent SLN biopsy using the MIPS at Kyoto University Hospital from April to December 2020 were included in the study. The primary endpoints were the identification rate of SLNs and detection of positive SLNs by the MIPS. The secondary endpoint was the number of SLNs excised using the MIPS per patient. We also conducted a questionnaire survey focused on the utility of the MIPS; it involved doctors with an experience in using the MIPS. RESULTS: Seventy-nine patients (84 procedures) were included in the study. In 60 (71%) procedures, both the radioisotope (RI) method and MIPS were used. At least one SLN could be detected by the MIPS in all the procedures, with an identification rate of 100% (95% confidence interval 95.6-100%). A total of 19 (7%) positive SLNs were removed, which were identifiable by the MIPS. Among 57 patients in whom the MIPS and RI methods were used, there was no positive SLN only identified by the RI method. The results of the questionnaire survey showed that the MIPS enabled the operator and assistant to share the ICG fluorescence image in the surgical field and to communicate with each other easily. CONCLUSION: The current study demonstrated that the identification rate of SLNs using the MIPS was high, and the MIPS can be used for detecting positive SLNs. It was suggested that the MIPS will be useful in learning SLN biopsy procedures.

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population.

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction.