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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.

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-naive 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.

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, Combination of major clinicopathological risk factors and predictive scores could help identify and characterize high‐risk population carrying BRCA1/2 PGVs among Japanese breast cancer patients. Significant associations were found between the presence of PGVs and early disease onset, number of familial cancer cases within third‐degree relatives, triple‐negative breast cancer patients under the age of 60, and ovarian cancer history (all P

Introduction The new-generation QuantiFERON (QFT)-TB Gold Plus (QFT-Plus) is expected to be useful because it includes a new peptide that is supposed to induce a CD8+ T cell response. There is a need for a new marker with sensitivity higher than that of the conventional IFN-γ release assays owing to false-negative results in the latter. This study aimed to compare cytokines in QFT-plus and QuantiFERON-Gold In-Tube (QFT-GIT) supernatants to discriminate between active tuberculosis and latent tuberculosis infection (LTBI). Methods A cross-sectional study was conducted at Tokyo National Hospital, wherein 21 LTBI patients and age and sex-matched active TB patients were randomly selected. The levels of various cytokines were measured and compared using the MAGPIX System, and receiver operating characteristic (ROC) curves were generated. Results IL-1RA, IFN-γ, CXCL10/IP-10, and CCL4/MIP-1β levels were higher in the active TB group than in the LTBI group in QFT-GIT antigen (GIT Ag) tubes. In QFT-plus tubes, IL-1RA was higher in TB1 and TB2 tubes, while CCL2/MCP-1 was higher only in TB2 tubes. In Nil tubes, CCL5/RANTES, TNF-α, PDGF-BB, and IL-2 levels were significantly higher in the active TB group. IL-1RA in GIT Ag tubes showed the highest area under the curve of 0.8367. The sensitivity and specificity of IL-1RA were 66.7% (95% confidence interval [CI]: 43.0–85.4) and 90.5% (95% CI: 69.6–98.8), respectively, which were the highest among the cytokines. Conclusions IL-1RA level in the QFT-GIT supernatant can be a good marker for discriminating active TB from LTBI.

Objectives This study evaluated the efficacy of the following interferon (IFN)-γ release assays (IGRAs): QuantiFERON-TB Gold Plus (QFT-Plus), QFT-Gold In-Tube (QFT-GIT), and T-SPOT. TB (T-SPOT) with the quantitative values of IFN-γ response. Methods Blood samples were collected from patients with active tuberculosis (TB), latent TB infection (LTBI), individuals with previous TB infection, and healthy volunteers enrolled between May 2017 and June 2018. Results IGRAs results were analyzed in 175 subjects (76 had active TB, 14 had LTBI, 35 had prior TB infection, and 50 were healthy). QFT-Plus and QFT-GIT revealed equal efficacy for IFN-γ values, and the IFN-γ response in QFTs tended to increase with the spot counts in T-SPOT, with similar high sensitivities (approximately 90%) in the active TB group. The test concordance of two of three IGRAs was optimal among all subjects (κ coefficients: 0.82–0.96). Additionally, the median quantitative values of IFN-γ with QFT-Plus and QFT-GIT were higher in the active TB group than in the LTBI and previous TB groups. Conclusion Three IGRAs showed equivalent efficacy with high sensitivities and higher IFN-γ response in active TB group than that in non-active TB group.

Objectives Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. Design Retrospective cohort study from July 2010 to March 2017. Setting More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. Patients The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. Interventions We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). Measurements and main results A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. Conclusions Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Background: Breast cancer risk models are used to predict the risk of carrying a variant, for one of the most common breast cancer susceptibility genes such as BRCA1 and BRCA2, and the lifetime risk of developing breast cancer. The prediction of harboring a germline variant of the BRCA gene and the development of breast or ovarian cancer over time affects the decision-making for undergoing genetic testing and screening using imaging techniques as the common practice. For instance, the American Cancer Society and the National Comprehensive Cancer Network (NCCN) recommends screening using MRI in women with 20% or greater lifetime risk of having breast cancer. We aimed to investigate the prediction of these risks in Japanese women, particularly on the relationship between the presence of pathogenic germline variants and breast cancer susceptibility genes, using a cohort of 1016 primary breast cancer patients. Patients and Methods: We analyzed a cohort of Japanese patients with primary breast cancer who were treated at the Kyoto University Hospital and the related institutions or hospitals from the period of 2011 to 2016. The germline variants were examined for a set of 13 breast cancer susceptibility genes, using targeted-capture sequencing of pooled DNA, and it was found that 66 out of 1016 patients had pathogenic variants. These included 11 functionally well-established genes (BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, NF1, PALB2, ATM, CHEK2, and NBN) and two additional genes (BARD1 and BRIP1), which are recommended for the screening of high-risk patients with hereditary breast cancer in the NCCN guidelines. Using this cohort, we studied the association of the calculated risk of carrying a germline variant of BRCA1/ BRCA2, using the Tyrer-Cuzick model Breast Cancer Risk Evaluation Tool, within the laboratory germline test results. Results: Pathogenic germline variants of BRCA1/ BRCA2 were carried by 54 (5.3%) out of the 1016 patients (12 cases of BRCA1 and 42 cases of BRCA2). According to the NCCN guidelines, which focus on Genetic/ Familial High-Risk Assessment: Breast and Ovarian, it was found that 500 out of 1016 (49.2%)patients were categorized for considering germline testing. In fact, 38 (7.6%) of the 500 patients, harbored a pathogenic germline variant of BRCA1/ BRCA2. In the remaining 516 patients, 16 (3.1%) harbored the pathogenic germline variant of BRCA1/ BRCA2. The predictive risks of the Tyrer-Cuzick model Breast Cancer Risk Evaluation Tool were recorded as follows: Area under the ROC curve, BRCA1 (area 0.750, 95% CI- 0.581-0.919), BRCA2 (area 0.741, 95% CI- 0.661-0.820), BRCA1 or BRCA2 (Area 0.749, 95% CI: 0.675-0.822), suggesting that the Tyrer-Cuzick model may be useful for the Japanese population. In the mammography breast density analysis, 484 patients showed almost entirely fat or scattered fibroglandular breast tissue, and 362 cases had heterogeneous or extreme fibroglandular breast tissue. In this study, the correlations of breast tissue density with age and breast or ovarian cancer familial history have been reported in greater detail. Discussion and Conclusions: In a retrospective cohort of 1016 Japanese patients with primary breast cancer, 5.3% had pathogenic germline variants of BRCA1/ BRCA2. In a group recommended by NCCN guidelines for considering genetic testing, the BRCA1/ BRCA2 variant rate was 7.6%. Predictive risks calculated by the Tyrer-Cuzick model similar with the known data. Further data are reported. Citation Format: Noriko Senda, Nobuko Kawaguchi-Sakita, Masahiro Kawashima, Yukiko Inagaki-Kawata, Kenichi Yoshida, Tomomi Nishimura, Masahiro Takada, Eiji Suzuki, Yuki Kataoka, Fumiaki Sato, Yoshiaki Matsumoto, Masae Torii, Hiroshi Yoshibayashi, Kazuhiro Yamagami, Shigeru Tsuyuki, Akira Yamauchi, Nobuhiko Shinkura, Hironori Kato, Yoshio Moriguchi, Ryuji Okamura, Norimichi Kan, Hirofumi Suwa, Shingo Sakata, Susumu Mashima, Fumiaki Yotsumoto, Tsuyoshi Tachibana, Mitsuru Tanaka, Takashi Inamoto, Masahiro Sugimoto, Seishi Ogawa, Masakazu Toi. Relationship between predicted risks of carrying breast cancer susceptibility genes and the presence of germline variants in Japanese patients with primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-12.

Background The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging mass spectrometry (MALDI-IMS). Methods We visualised the histological distribution of PIs containing different FAs in 65 primary breast cancer tissues using MALDI-IMS and investigated its association with clinicopathological features and gene expression profiles. Results Normal ductal cells (n = 7) predominantly accumulated a PI containing polyunsaturated FA (PI-PUFA), PI(18:0/20:4). PI(18:0/20:4) was replaced by PIs containing monounsaturated FA (PIs-MUFA) in all non-invasive cancer cells (n = 12). While 54% of invasive cancer cells (n = 27) also accumulated PIs-MUFA, 46% of invasive cancer cells (n = 23) accumulated the PIs-PUFA, PI(18:0/20:3) and PI(18:0/20:4). The accumulation of PI(18:0/20:3) was associated with higher incidence of lymph node metastasis and activation of the PD-1-related immune checkpoint pathway. Fatty acid-binding protein 7 was identified as a putative molecule controlling PI composition. Conclusions MALDI-IMS identified PI composition associated with invasion and nodal metastasis of breast cancer. The accumulation of PI(18:0/20:3) could affect the PD-1-related immune checkpoint pathway, although its precise mechanism should be further validated.

Objective Intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) frequently present with similar clinical, endoscopic and pathological features, therefore it is difficult to differentiate between them. The aim of this study was to elucidate the diagnostic delay and prognosis of ITB cases, initially misdiagnosed as IBD. Methods ITB cases were selected from the hospitalized patient list between April 2004 and March 2017 in a tuberculosis center in Japan. We retrospectively evaluated the initial diagnosis, clinical characteristics, endoscopic and pathological findings, bacterial examinations, treatment and prognosis. Results Among 66 ITB patients, ten patients were initially misdiagnosed as IBD. Seven patients were male and the median age was 60.5 years (23-74 years). After the diagnosis of IBD, all the patients were treated with mesalazine, in addition to corticosteroids in two patients and sequential azathioprine and infliximab in one. The median duration of diagnostic delay was 5.5 months (range 0.5-17 months). Eight patients had active pulmonary tuberculosis at the diagnosis of ITB. Acid-fast bacilli were confirmed in four of seven patients by reevaluation of the pathological specimens at the IBD diagnosis. Two patients needed intestinal resection and one with erroneous corticosteroid use for IBD died due to respiratory failure in spite of receiving appropriate treatment for tuberculosis. Conclusion ITB patients were frequently misdiagnosed and treated as IBD, thus resulting in a poor clinical outcome even after finally making a correct diagnosis and administering appropriate treatment. On diagnosis of IBD and/or treatment failure, chest radiograph and acid-fast bacilli of the pathological specimens should be carefully evaluated in order to rule out tuberculosis.

BackgroundThe 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.MethodsThis 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.ResultsSeventy-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.ConclusionThe 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.

This study aimed to evaluate the predictions of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prognosis of triple-negative breast cancer (TNBC), especially with residual disease (RD) after preoperative chemotherapy. This retrospective analysis included 74 TNBC patients who received preoperative chemotherapy. DCE-MRI findings from three timepoints were examined: at diagnosis (MRIpre), at midpoint (MRImid) and after chemotherapy (MRIpost). These findings included cancer lesion size, washout index (WI) as a kinetic parameter using the difference in signal intensity between early and delayed phases, and time-signal intensity curve types. Distant disease-free survival was analysed using the log-rank test to compare RD group with and without a fast-washout curve. The diagnostic performance of DCE-MRI findings, including positive predictive value (PPV) for pathological responses, was also calculated. RD without fast washout curve was a significantly better prognostic factor, both at MRImid and MRIpost (hazard ratio = 0.092, 0.098, p mid was 76.7% by the cut-off point at negative WI value or lesion size = 0, and 66.7% at lesion size = 0. WI and curve types derived from DCE-MRI at the midpoint of preoperative chemotherapy can help not only assess tumour response but also predict prognosis.

Yellow nail syndrome (YNS) is a rare entity characterized by thickened yellowish nails, lymphedema and respiratory manifestations such as pleural effusion. Lymphatic dysfunction is considered as a cause of YNS. However, evidence of systemic dilatation/hyperplasia of lymphatics based on autopsy in YNS is not available. In this report, autopsy revealed dilatation and hyperplasia of lymphatic vessels in lungs, visceral and parietal pleurae, and intestines. We identified the direct opening of lymphatic vessels of the visceral pleura to the pleural cavity, which indicated the pathophysiology of uncontrollable pleural effusion in YNS. The current case was compromised with primary biliary cholangitis (PBC). The onset of PBC seemed to be related with the progression of YNS.

The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants., 遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.

Molecular-targeted drugs (MTDs), such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase inhibitors, are used to treat non-small-cell lung cancer (NSCLC). The incidence of rash caused by EGFR-TKIs and discontinuation of MTDs because of rash are issues. Rapid desensitization therapy (RDT) was performed in five patients who developed severe rash after introduction of MTDs and was successful in four, all of whom showed no rash relapse. RDT may thus be useful for treating rash in patients receiving MTDs for NSCLC.

Most cases of lymph node enlargement after completing tuberculosis (TB) treatment are due to paradoxical reaction (PR), not relapse, and therefore, do not require re‐treatment. We herein report a case of a 28‐year‐old man who had developed cervical TB lymphadenitis and exhibited re‐enlargement of the same lymph nodes one month after completing effective TB chemotherapy, which was microbiologically proven as relapse. The patient noticed painful cervical lymphadenopathy one month after completion of chemotherapy for TB lymphadenitis. Combination chemotherapy with multiple anti‐TB drugs was resumed with suspicion of relapse. But, with his symptoms having worsened, surgical excision was performed. Mycobacterium tuberculosis was cultured from the dissected lymph nodes. Early regrowth of the lymph nodes after completing treatment can derive from microbiological relapse, in addition to PR. Surgical excision was useful for the microbiological diagnosis of the relapse. We must take care of lymph node re‐enlargement in consideration of TB relapse., Most cases of lymph node enlargement after completing tuberculosis (TB) treatment are due to paradoxical reaction (PR), not relapse, and therefore, do not require re‐treatment. We herein report a case of a 28‐year‐old man who had developed cervical TB lymphadenitis and exhibited re‐enlargement of the same lymph nodes one month after completing effective TB chemotherapy, which was microbiologically proven as relapse.

The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.Aspergillus fumigatus can acquire azole resistance during long-term treatment with azole drugs in patients with chronic pulmonary aspergillosis (CPA). The aim of this study was to determine the detection rate of azole-resistant A. fumigatus (ARAF) in isolates from CPA patients who had been treated with azoles. In addition, a potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104). The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF from all isolates was 8.3% (n = 10). Greater than 10% of the 47 isolates obtained from 36 CPA patients who had been treated with azoles exhibited resistance. Furthermore, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients undergoing long-term azole treatment at the time of antifungal therapy failure.

This study aimed to identify the characteristics of the vascular network in the superficial subcutaneous layer of the breast and to analyze differences between breasts with cancer and contralateral unaffected breasts using vessel branching points (VBPs) detected by three-dimensional photoacoustic imaging with a hemispherical detector array. In 22 patients with unilateral breast cancer, the average VBP counts to a depth of 7 mm below the skin surface were significantly greater in breasts with cancer than in the contralateral unaffected breasts (p

Granulocyte-colony-stimulating factor (G-CSF) production in carcinomas is associated with a very aggressive phenotype. Interleukin (IL)-17 secreted from tumor-infiltrating lymphocytes induces the production of G-CSF and vascular endothelial growth factor (VEGF) in cancer tissue. We present a case of a G-CSF-producing metaplastic breast carcinoma (MpBC) accompanied by systemic elevation of IL-17 and VEGF levels. A 56-year-old woman presented with a rapidly growing tumor measuring > 10 cm in her left breast. Core needle biopsy confirmed the diagnosis as MpBC with triple-negative features. Diffuse fluorodeoxyglucose uptake in the long bones and marked leukocytosis suggested that the G-CSF was produced by the primary tumor, which showed upregulated G-CSF mRNA and protein levels. Multiplex cytokine assessment identified increased serum IL-17, VEGF, and G-CSF levels. After radical mastectomy and skin grafting, the leukocyte count and serum G-CSF, IL-17, and VEGF levels were normalized. She underwent postmastectomy radiotherapy (50 Gy/25 Fr) and adjuvant chemotherapy (90 mg/m(2) of epirubicin and 600 mg/m(2) of cyclophosphamide followed by 80 mg/m(2) of paclitaxel) and is alive without recurrence. This is the first in vivo observation that describes the systemic elevation of IL-17 and VEGF levels with concomitant G-CSF production. Further research is warranted to study the IL-17/G-CSF/VEGF axis as a potential therapeutic target for this aggressive type of breast cancer.

Background: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates pulmonary NTM infection, high mortality has been reported in case reports and small studies. Objectives: The purpose of this study was to clarify the clinical features and treatment outcomes of pulmonary NTM infection cases accompanied by NTM pleuritis. Methods: Medical records of 1,044 patients with pulmonary NTM disease were retrospectively reviewed to select patients complicated by NTM-proven pleuritis. We investigated clinical characteristics, pathogens, pleural effusion examinations, radiographic findings, treatments, and clinical course of the NTM pleuritis patients. Results: Among 1,044 cases with pulmonary NTM, NTM pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were complicated by pneumothorax. Subpleural cavities were radiologically detected in 11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases (93.3%). Eleven patients were treated with combinations of 2–4 antimycobacterial drugs, including clarithromycin, and 2 patients were treated with isoniazid, rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and surgical approach was added in 6 cases. The pleural effusion of 2 patients treated with only antimycobacterial medications gradually deteriorated. Two patients died from NTM pleuritis, and 1 patient died from pneumonitis during a mean of 1.8 years of follow-up. Conclusions: Comorbid NTM pleuritis was difficult to treat by medical therapy alone and resulted in a poor prognosis. In addition to antimycobacterial agents, chest tube drainage and surgical procedures in the early stages should be considered to treat NTM pleuritis.

A combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is effective for some peritoneal malignancies. However, the indications for elderly patients remain unclear, with substantial postoperative morbidity and mortality being problematic. Clinical data were analyzed in 42 patients undergoing CRS + HIPEC for peritoneal malignancy. The primary tumor was located in the appendix in 32 cases and elsewhere in 10 cases. Operative results and survival data were compared between patients aged ≥70 and

Introduction: Interferon-gamma (IFN-γ) response wanes by years after tuberculosis infection. CD8+ T cells play a role to control tuberculosis infection mainly in active phase, and also in chronic phase. IFN-γ response by years after tuberculosis (TB) infection measured with QuantiFERON-TB Plus (QFT-Plus) has not been reported. Aims: To evaluate IFN-gamma response by years after TB infection with QFT-Plus. Materials and Methods: From May 2017 to June 2018, we enrolled 36 subjects with previous active TB and divided into 2 groups: the subjects who was diagnosed with TB within 3 years (group 1, n=18) and over 3 years before (group 2, n=18). Positive rate and quantitative IFN-γ response with QFT-Plus were compared among two groups. Results: The average age was 56.6±19.5 years in group 1 and 66.2±15.5 years in group 2, and 13 (72.2 %) were male in both groups. The median years after active TB onset was 1.3 (0.5–2.4) years in group 1 and 11.2 (3–70) years in group 2. Positive rate with QFT-Plus was 83.3% and 55.6%, respectively. The quantitative IFN-γ response was 0.86 (0.01–11.52) and 0.49 (0.01–5.33), respectively. The difference in quantitative values between TB2 and TB1 (TB2-TB1: surrogate CD8+ T cells response) were 0.10 (-0.72–2.46) in group 1 and 0.00 (-1.03–1.54) in group 2. The positive rate, the quantitative IFN-γ response, and TB2-TB1 value were lower in group 2, although there was no significant difference. Conclusion: These results suggested that IFN-γ response might wane over 3 years after TB infection. The median of TB2-TB1 values in group 2 were zero, suggesting CD8+ T cells response might be weaker over 3 years after TB infection.

Introduction: In Japan, poor general condition related with old age and complications may affect the prognosis of patients with tuberculosis (TB). Though spontaneous pneumothorax (SP) is known as a complication of pulmonary TB, few reports on this topic have been available. Aims: To evaluate clinical features of SP in patients with TB. Materials and Methods: Based on medical records, we diagnosed 81 patients with SP out of the 2384 patients at our TB-referral hospital from 2011 to 2016, analyzed clinical features and compared with randomly selected 81 patients without SP. Results: The patients with SP demonstrated significantly higher age (73y, range 30-91 y vs 69y, range 19-94 y, P=0.0128), more male patients (n=68, 83.9% vs n=51, 62.9%, P=0.0025), higher positive rate of acid-fast bacilli in sputum smear, (n=75, 92.6% vs n=59, 72.8%, P=0.0009), more cavitation (n=54, 66.7% vs n=32, 39.5%, P=0.0005) and higher mortality rate (37% vs 14%), compared with the patients without SP. Thirty-nine patients with SP (48.1%) required chest-tube insertion, including 26 patients (66.7%) with successful chest-tube drainage and 13 unsuccessful and deceased patients. Conclusion: These results suggested that the patients with SP were associated with severe TB and had poor prognosis.

Background: In patients with suspected pulmonary tuberculosis, who have difficulty in expectorating sputum, alternative specimens by invasive procedures, gastric aspirate or sputum suction, are not always available in the feeble elderly. Several studies report the benefit of stool test for pediatric or HIV infected patients, but few in adult patients. Objective: To evaluate the benefit of stool examination as non-invasive alternative test to detect Mycobacterium tuberculosis (MTB) infection. Methods: Stool specimens were examined for mycobacteria in 187 cases of microbiologically-diagnosed pulmonary tuberculosis between September 2013 and August 2017. We retrospectively reviewed the medical records to determine the positive detection rate of MTB with stool specimens and investigated factors related to MTB detection. Results: Among 187 patients included, positive rate of MTB in stool was 12.8% (24/187) by stool acid-fast bacilli smear, 68.1% (98/144) by TRC Rapid®, and 40.6% (76/187) by culture. Multivariate logistic regression analysis revealed two contributing factors to MTB detection in stool; cavitation and male. The adjusted odds ratio with 95% confidence interval (CI) for cavitation was 2.9 (95%CI 1.48–5.69) and 2.1 (95%CI 1.08–3.93) for male. Conclusion: We recommend stool examination for those who are unable to give sputum and have risks for invasive procedures. Keywords: Stool, Tuberculosis, Diagnosis

Combined pulmonary fibrosis and emphysema (CPFE) is a common but under-recognized syndrome characterized with distinct profiles of both pulmonary fibrosis and emphysema. Pulmonary hypertension (PH) is particularly prone to develop as a common complication, leading to exercise limitation and worse prognosis of CPFE. Although the therapy of patients with PH from CPFE cannot be endorsed, an individual treatment may be considerable when accompanying severe PH. We report a case of a 71-year-old male with PH from CPFE, who improved pulmonary arterial compliance (PAC) and exercise capacity in response to pulmonary vasodilator. Keywords: Combined pulmonary fibrosis and emphysema, Pulmonary hypertension, Pulmonary arterial compliance, Pulmonary vasodilator

Summary Objectives Interferon-gamma release assays (IGRAs) can be positive in patients infected with Mycobacterium kansasii (M. kansasii) , which carries some of Mycobacterium tuberculosis specific antigens adopted for IGRAs. Our aim is to evaluate positive rate and factors associated with positive IGRAs in patients with M. kansasii pulmonary infection. Methods We retrospectively investigated 105 M. kansasii cases in which IGRAs were performed before or ≦14 days after treatment initiation. Clinical characteristics including a history of tuberculosis, radiographic features and laboratory data were collected from medical records. Results Positive rate of each IGRA was 25.9% (15/58) in QuantiFERON TB-Gold (QFT-G), 31.8% (7/22) in QuantiFERON-TB Gold In Tube (QFT-GIT), and 33.3% (7/21) in T-SPOT. TB (T-SPOT). After excluding cases having a history of tuberculosis, positive rate of each IGRA decreased to 19% (8/42) in QFT-G, 20% (3/15) in QFT-GIT, and 18.8% (3/16) in T-SPOT. The multivariate analysis revealed that only previous tuberculosis was significantly associated with positive IGRAs (odds ratio, 4.758; 95% confidence interval, 1.73–13.05; p = 0.002). Conclusions Positive rates of IGRAs were low in patients with M. kansasii , especially in those without previous tuberculosis. M. kansasii pulmonary infection alone might induce less interferon-gamma production with the antigens.

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) for elderly people has been included in the National Immunization Program (NIP) of Japan since October 2014. Targets for PPSV23 were restricted to persons ≥65 years of age and persons 60 to 64 years of age with an underlying severe physical disability (expressed as 1st grade in Japan). In this study, the clinical courses of non-target persons

Mycobacterium shinjukuense lung disease was diagnosed in 3 men and 3 women [mean age: 77.0±12.2 (57-93) years]. On imaging, 3 patients with previous pulmonary tuberculosis exhibited a fibrocavitary pattern, while the other 3 patients showed nodular bronchiectasis. A test with a tuberculosis rRNA identification kit (TRC Rapid(®) M. TB) was falsely positive for M. tuberculosis due to DNA sequence similarity in 16SrRNA. M. shinjukuense was identified by the gene sequences of rpoB, 16S rRNA, and hsp65. The symptoms and imaging findings of most of the patients have improved with chemotherapy with low minimum inhibitory concentrations of anti-tuberculosis drugs.

e12631 Background: Residual disease after preoperative chemotherapy is known to be a poor prognostic factor in triple-negative breast cancer (TNBC). Perioperative use of cisplatin (CDDP) is a well-known, standard treatment for most tumors except breast cancer. In this study, we explore the long-lasting anti-tumor activity of CDDP for TNBC patients. Methods: This research was based on consecutive study of seventy-nine previously untreated stage I–III TNBC patients treated with or without CDDP-based preoperative chemotherapy from 2007 to 2018 at the Kyoto University Hospital. We calculated the residual cancer burden (RCB) using the RCB calculator. All patients were sorted according to their RCB class: the pathological complete response (pCR), and RCB class I (minimal), II (moderate) or III (extensive). Distant disease-free survival (DDFS) was analyzed using the Kaplan-Meier method. Using mass spectrometry, we measured platinum concentrations in serum and normal breast tissue removed during surgery from patients treated with any platinum agents. We examined multiplex cytokine assays from serum sequentially, comparing CDDP and non-CDDP groups. Results: Forty-seven cases were treated with CDDP, and thirty-two did not have CDDP. The pCR rate was 53.2% for the CDDP group and 21.9% without CDDP. Patients with pCR and RCB class I were all distant disease-free. There was no significant difference between each RCB class using CDDP. However, patients belonging to RCB classes II and III with CDDP showed a better prognosis than the same RCB classes without CDDP (hazard ratio = 0.12). Platinum concentrations in serum were correlated with the time from the last dose of platinum agents, but platinum was even detected in serum two years after CDDP. No significant difference was found in the platinum concentrations of serum or normal breast tissue in the pCR and non-pCR groups. We also found that there were significant cytokine expression alteration related to T-cell infiltration only in the CDDP group one year after operation. It is suggested that CDDP may even affect the systemic immune alteration one year after operation. Conclusions: Our data shows that CDDP- based chemotherapy improves DDFS in patients with a substantial residual tumor. CDDP seems to sustain anti-tumor activity for a number of years and interaction with the systemic immune alteration.

Hemoptysis is a common symptom associated with chronic pulmonary aspergillosis (CPA). While surgery is the primary choice to manage hemoptysis, it is often avoided because patients with CPA are more likely to have complications such as respiratory insufficiency and low pulmonary function. Bronchial artery embolization (BAE) may be considered one of the treatments of massive and persistent hemoptysis for such patients.We retrospectively reviewed medical records of 41 patients, admitted to National Hospital Organization Tokyo National Hospital, Tokyo, Japan with hemoptysis arising from CPA between January 2011 to December 2016, who were considered inoperable and had undergone BAE.Out of the 41 cases analyzed in this study, 21 (51.2%) developed rebleeding after BAE within the mean follow-up duration of 24 months. The non-rebleeding rate of patients after BAE was 92.7% within a month and 65.8% within a year. Patients who developed rebleeding had significantly more non-bronchial systemic arteries responsible for the bleeding compared with patients who did not develop rebleeding (mean of 2.55 vs. 4.86, respectively, P = 0.011). Patients with stable or improved radiological findings demonstrated significantly lower rebleeding rates than those with radiological deterioration (P0.001). The non-rebleeding patients had significantly better survival than those with rebleeding (79.7% vs. 39.9% over 5 years, P = 0.046).Bronchial artery embolization was effective in controlling hemoptysis in patients with CPA, especially those who could not undergo surgical resection. However, disease control of CPA was important to prevent rebleeding over the long term and to improve survival after BAE.

Purpose There have been scarce data evaluating the differences of clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) depending on underlying pulmonary diseases. We tried to clarify them in CPA patients who had pulmonary emphysema or previous pulmonary tuberculosis. Methods We reviewed and evaluated CPA patients diagnosed between 2007 and 2013 with pulmonary emphysema (PE group; n = 29), with previous pulmonary tuberculosis (PT group; n = 47) and with combination of these 2 underlying conditions (CTE group; n = 24). Results In CT findings, fungus balls were rare in PE group (7% in PE group and 36% in PT group; p = 0.006). Compared with PT group, PE group patients exhibited more frequent preceding antibiotics administration (45% vs 11%; p = 0.002) and fever (52% vs 17%; p = 0.002), less frequent hemosputum (24% vs 57%; p = 0.008), and more frequent consolidations in imaging (79% vs 38%; p = 0.001) and respiratory failure (34% vs 13%; p = 0.020), possibly suggesting more acute clinical manifestations of CPA in emphysematous patients. Trend of the differences between PT and PE group was not changed when patients with fungal balls were excluded. Multivariate Cox regression analysis of risks for all-cause mortality revealed age (HR, 1.079; p = 0.002) and emphysema (HR, 2.45; p = 0.040) as risk factors. Conclusions Assessment of underlying lung diseases is needed when we estimate prognosis and consider treatment of CPA patients. Particularly, emphysematous patients can be presented as refractory pneumonia and show poor prognosis.

A 60-year-old man was admitted to our hospital because of a persistent fever with enlargement of multiple lymph nodes in the mediastinum and around the pancreatic head. He was diagnosed with tuberculosis and human immunodeficiency virus infection. We started antiretroviral therapy three weeks after the initiation of anti-tuberculous therapy. Two weeks later, jaundice appeared with dilatation of the biliary tract due to further enlargement of the lymph nodes, which seemed to be immune reconstitution inflammatory syndrome (IRIS). The administration of corticosteroids resolved the obstructive jaundice without surgical treatment or endoscopic drainage. Obstructive jaundice caused by IRIS should first be treated with corticosteroids before invasive treatment.

Pleomorphic carcinoma (PC) is a rare malignant lung tumor with a poorer prognosis compared to other histological types of non-small cell lung cancer. However, several recent immunohistochemical studies revealed that a low MIB-1 index is a good prognostic marker in patients with PC. We report the case of a patient with PC and a single brain metastasis that achieved long-term recurrence-free survival following treatment with combined modality therapy. In this case, the MIB-1 index was reduced by gemcitabine-based chemotherapy, which may have led to long-term disease-free survival. The MIB-1 index may be a useful biomarker for the response to chemotherapy.

Species of Aspergillus section Nigri are generally identified by molecular genetics approaches, whereas in clinical practice, they are classified as A. niger by their morphological characteristics. This study aimed to investigate whether the species of Aspergillus section Nigri isolated from the respiratory tract vary depending on clinical diagnosis. Forty-four Aspergillus section Nigri isolates isolated from the lower respiratory tracts of 43 patients were collected from February 2012 to January 2017 at the National Hospital Organization (NHO) Tokyo National Hospital. Species identification was carried out based on β-tubulin gene analysis. Drug susceptibility tests were performed according to the Clinical and Laboratory Standards Institute (CLSI) M38 3rd edition, and the clinical characteristics were retrospectively reviewed. A. welwitschiae was isolated most frequently, followed by A. tubingensis. More than half of the A. tubingensis isolates exhibited low susceptibility to azoles in contrast to only one A. welwitschiae isolate. Approximately three quarters of the patients from whom A. welwitschiae was isolated were diagnosed with colonization, whereas more than half the patients from whom A. tubingensis was isolated were diagnosed with chronic pulmonary aspergillosis (CPA). More attention needs to be given to the drug choice for patients with CPA with Aspergillus section Nigri infection because A. tubingensis, which was found to be frequently azole-resistant, was the most prevalent in these patients., Medical mycology, 58(3), pp.310-314; 2020

High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is an emerging application for lipid research that provides a comprehensive and detailed spatial distribution of ionized molecules. Recent lipidomic approach has identified several phospholipids and phosphatidylinositols (PIs) are accumulated in breast cancer tissues and are therefore novel biomarker candidates. Because their distribution and significance remain unclear, we investigated the precise spatial distribution of PIs in human breast cancer tissues using high-resolution MALDI IMS. We evaluated tissues from nine human breast cancers and one normal mammary gland by negative ion MALDI IMS at a resolution of 10 μm. We detected 10 PIs with different fatty acid compositions, and their proportions were remarkably variable in the malignant epithelial regions. High-resolution imaging enabled us to discriminate cancer cell clusters from the adjacent stromal tissue within epithelial regions; moreover, this technique revealed that several PIs were specifically localized to cancer cell clusters. These PIs were heterogeneously distributed within cancer cell clusters, allowing us to identify two different populations of cancer cells that predominantly expressed either PI(18:0/18:1) or PI(18:0/20:3). Tracing the expression level of PIs during cancer cell progression suggested that the latter population is associated with the invasion. Our study documents a novel model for phospholipid analysis of breast cancer tissues by using high-resolution MALDI IMS and identifies candidate PIs that can describe a specific phenotype of cancer cells.

Background Circulating cell-free DNA (cfDNA) has recently been recognized as a resource for biomarkers of cancer progression, treatment response, and drug resistance. However, few have demonstrated the usefulness of cfDNA for early detection of cancer. Although aberrant DNA methylation in cfDNA has been reported for more than a decade, its diagnostic accuracy remains unsatisfactory for cancer screening. Thus, the aim of the present study was to develop a highly sensitive cfDNA-based system for detection of primary breast cancer (BC) using epigenetic biomarkers and digital PCR technology. Methods Array-based genome-wide DNA methylation analysis was performed using 56 microdissected breast tissue specimens, 34 cell lines, and 29 blood samples from healthy volunteers (HVs). Epigenetic markers for BC detection were selected, and a droplet digital methylation-specific PCR (ddMSP) panel with the selected markers was established. The detection model was constructed by support vector machine and evaluated using cfDNA samples. Results The methylation array analysis identified 12 novel epigenetic markers (JAK3, RASGRF1, CPXM1, SHF, DNM3, CAV2, HOXA10, B3GNT5, ST3GAL6, DACH1, P2RX3, and chr8:23572595) for detecting BC. We also selected four internal control markers (CREM, GLYATL3, ELMOD3, and KLF9) that were identified as infrequently altered genes using a public database. A ddMSP panel using these 16 markers was developed and detection models were constructed with a training dataset containing cfDNA samples from 80 HVs and 87 cancer patients. The best detection model adopted four methylation markers (RASGRF1, CPXM1, HOXA10, and DACH1) and two parameters (cfDNA concentration and the mean of 12 methylation markers), and, and was validated in an independent dataset of 53 HVs and 58 BC patients. The area under the receiver operating characteristic curve for cancer-normal discrimination was 0.916 and 0.876 in the training and validation dataset, respectively. The sensitivity and the specificity of the model was 0.862 (stages 0-I 0.846, IIA 0.862, IIB-III 0.818, metastatic BC 0.935) and 0.827, respectively. Conclusion Our epigenetic-marker-based system distinguished BC patients from HVs with high accuracy. As detection of early BC using this system was comparable with that of mammography screening, this system would be beneficial as an optional method of screening for BC. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0788-z) contains supplementary material, which is available to authorized users.

Introduction: One of the emerging problems is that the percentage of azole-resistant A. fumigatus is increasing worldwide. There are few reports clearly indicating azoles are clinically ineffective to azole-resistant A. fumigatus with chronic pulmonary aspergillosis (CPA) patients. Aims: To test the hypothesis that treatment outcome is poorer in CPA patients with azole-resistant A.fumigatus than in those with azole-sensitive. Materials and Methods: We retrospectively reviewed medical records of 64 CPA patients with isolation of A. fumigatus. From 2012 to 2015, 75 isolates from these patients were identified as A. fumigatus with genetic analysis of internal transcribed spacer, Domein 1/Domein 2 and β-tubulin. Susceptibility test for antifungal drugs was performed by Clinical and Laboratory Standards Insitute•M38-2. Results: There were 4 itraconazole (ITCZ) resistant isolates (5.3%) and 2 voriconazole (VRCZ) resistant isolates (2.7%). The 2 VRCZ resistant strains were also resistant to ITCZ. Three of 4 azole resistant A.fumigatus strains have CYP51A mutations(G448S, M220I, F219C). Azole-resistant A.fumigatus was isolated after long term ITCZ treatment. One of VRCZ resistant strain had not been treated with VRCZ, suggesting cross resistance. The effectiveness of ITCZ and VRCZ to CPA patients with azole sensitive A.fumigatus were 41% (11/27) and 75% (6/8) respectively. Azole antifungal drugs were ineffective for all 4 patients infected with azole-resistant A.fumigatus . Conclusion: This study suggests CPA by azole resistance A.fumigatus have poor treatment outcome with azole antifungal treatment.

Indocyanine green (ICG) fluorescence navigation is a useful option in sentinel node biopsy (SNB) for breast cancer. However, several technical difficulties still exist. Since the sentinel node (SN) cannot be recognized over the skin, subcutaneous lymphatic vessels (LVs) must be carefully dissected without injury. In addition, the dissecting procedures are often interrupted by turning off the operating light during fluorescence observation. In this report, we introduce a new approach using the axillary compression technique to overcome these problems. In the original procedure of the ICG fluorescence method, the subcutaneous lymphatic drainage pathway from the breast to the axilla was observed in fluorescence images, but no signal could be obtained in the axilla. When the axillary skin was compressed against the chest wall using a plastic device, the signals from the deeper lymphatic structures could be observed. By tracing the compression-inducible fluorescence signal towards the axilla, transcutaneous detection and direct approach to the SN were achieved. The benefit of this approach is that there is no risk of injury of LVs, and the procedures are interrupted less frequently by fluorescence observation. The axillary compression technique was used in 50 patients with early breast cancer. SNs were successfully removed in all patients. Transcutaneous detection and direct approach were possible in 47 patients. This approach was also effective in obese patients. Axillary compression technique is a simple way to facilitate the surgical procedures of ICG fluorescence-navigated SNB for breast cancer.

A 61-year-old female who underwent cytoreductive surgery for pseudomyxoma peritonei showed left pleural recurrence 2 years later. Disseminated tumors were widely observed in the whole parietal pleura, the lung surface and the diaphragm. Left parietal pleurectomy and decortications of the lung were performed. Intrathoracic chemotherapy with CDDP was added after resection. The postoperative course was uneventful, and the patient was discharged on the 33rd postoperative day. She has undergone repeat cytoreductive surgeries twice for abdominal recurrence to date. At 62 months after thoracic cytoreduction, she maintained a disease-free status with a good quality of life. This is the first report showing that long-term survival longer than 5 years was achieved with a disease-free state by pleurectomy and intrathoracic chemotherapy.

A 34-year-old woman visited the hospital suffering from enanthema of the tongue, hair loss, and nonproductive cough. Corticosteroid administration slightly resolved the enanthema and hair loss, but not the nonproductive cough. She was transferred to another hospital for the resection of a retroperitoneal mass, which was histopathologically diagnosed as unicentric, hyaline vascular type Castleman’s disease. She was then referred to our hospital due to progressive dyspnea and was diagnosed as having bronchiolitis obliterans based on computed tomography scan findings and a lung function test, while paraneoplastic pemphigus was clinically considered for her enanthema. After her death from respiratory failure in spite of corticosteroid administration, autopsy confirmed constrictive bronchiolitis in the lung. Mucocutaneous lesions, clinically considered as paraneoplastic pemphigus, were histologically different from pemphigus. The constrictive bronchiolitis and other pathological findings, including nonviral chronic hepatitis and interstitial nephritis, confirmed the diagnosis of paraneoplastic autoimmune multiorgan syndrome associated with the Castleman’s disease.

Background Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease.

In the 2011/2012 season, 18 patients were admitted to our hospital due to influenza virus A infection and the number had increased compared to the previous 3 years (average 5.3 patients/year). Therefore we evaluated the clinical characteristics, treatment, and prognosis of hospitalized cases. Although there were many reports on viral pneumonia caused by influenza (H1N1) 2009 among the young population in the 2009/ 2010 season, 16 out of 18 hospitalized patients were over 65 years-old in the 2011/2012 season. Major causes of admission were pneumonia in 8 cases, heart failure in 5 cases and bronchial asthma attack in 3 cases. The average age of 9 patients with pneumonia was higher significantly compared to 9 patients without pneumonia (average age 85.3 ± 10.2 : 71.4 ± 16.1, p < 0.05). Influenza vaccination was performed in 11 patients in total, and 6 out of 9 patients with pneumonia. The interval from illness onset to administration of neuraminidase inhibitors was 1.8 ± 1.1 days in cases with pneumonia and 2.1 ± 1.5 days in cases without pneumonia. Though 17 patients got well, one patient died from aspiration pneumonia after recovering from influenza A infection. In the 2011/2012 season, although many patients who had received vaccination needed to be hospitalized because of influenza A infection, the prognosis was fairly good.

An asymptomatic mediastinal abscess was incidentally found in a 68-year-old male patient with a long history of hemodialysis. He had never had any symptoms but complained of chest pain only after the abscess ruptured into the right thoracic cavity. The abscess was discovered incidentally, when computed tomography was performed to determine the cause of his increasing ascites. Video-assisted thoracic surgery was performed to facilitate sufficient drainage and safe debridement. After the operation, we administered adequate antibiotics and continued irrigation of the thoracic cavity. The origin of his abscess was still unknown, but we have to consider that immunocompromised patients including those undergoing hemodialysis can develop severe infectious conditions even with minor causes. This case is clinically suggestive of the need to focus on the immunocompromised condition of hemodialysis patients. Furthermore, our case reveals video-assisted thoracic surgery to be a safe and less invasive procedure for patients in poor general condition.

Background: Hemoptysis is sometimes a life threating condition and need to be treated urgently. Nearly 20% of hemoptysis cases were diagnosed as cryptogenic after clinical investigation. Objective: The purpose of this study was to clarify clinical and angiographic characteristics of cryptogenic hemoptysis (CH). Methods: We retrospectively reviewed medical records of 35 patients admitted to our hospital with CH from October 2010 to September 2014, who underwent bronchial artery embolization (BAE) using detachable coils. Results: In the 35 cases, the angiographic findings revealed that the diameter of bronchial arteries was less than 2 mm in 13 patients (37.1%), 2 to 3 mm in 17 (48.5%) and more than 3 mm in five (14.2%). Hypervasculization was detected in 29 patients (82.9%), small bronchial aneurysms were detected in eight (22.9%), and systemic pulmonary shunt was in two (5.7%). The amount of hemoptysis was slight ( 200 mL/day) in four patients and no obvious relationship was found between the diameter of bronchial arteries and the amount of hemoptysis. Twentyeight cases (80.0%) had the history of smoking and 24 cases (68.7%) were current smokers. BAE was successfully performed in 33 patients (94.3%) while bronchoscopic hemostatic therapy was added in one patient (2.8%) and BAE was not done in one patient (2.8%) because the bronchial artery was too narrow. In successful embolization group, non-rebleeding rate was 100% for 12 months. Conclusion: BAE was highly effective for the management of CH. Small bronchial aneurysms, undetected with CT angiography, were suspected as the cause in some cases.

Introduction: The 2007 ATS/IDSA statement for Mycobacterium avium complex (MAC) lung disease suggested that aminoglycoside antibiotics should be considered in addition to clarithromycin (CAM), rifampicin, and ethambutol for extensive fibrocavitary disease or patients deteriorated with prior medications. Aims: To evaluate efficacy and safety of kanamycin (KM) added to the patients with drug-refractory MAC infection. Methods: We selected patients with MAC pulmonary disease treated with kanamycin more than 3 months after deterioration with a standard therapy from 2010 to 2013. Patients with comorbid aspergillosis or simultaneous administration of quinolones were excluded. Medical records were retrospectively reviewed to evaluate symptomatic and radiographic improvement, sputum culture conversion and adverse effects. Results: The patients included were 11 males and 19 females with the median age of 66 years. The mean duration from the initiation of chemotherapy to KM addition was 5.83 years. CAM resistant MAC was isolated in 9 cases. Symptomatic improvement was indicated in 56.5% while radiographic abnormalities were improved in 15/29 (51.7%), stable in 11/29 (37.9%), and deteriorated in 3/29 (10.3%) 3 months later. Among 13 smear positive and 17 culture positive patients prior to KM addition, semi-quantitative count of sputum smear was decreased in 9 (69.2%) and sputum culture turned negative in 5 (29.4%). Side effects were rash (2 cases), renal dysfunction (2), hearing disorder (1), and eosinophilia (1). Conclusions: Addition of kanamycin is effective even after failure of initial chemotherapy and should be considered as a treatment option for drug-refractory MAC lung disease.

Background Hemoptysis frequently develops in patients with Mycobacterium avium complex (MAC) pulmonary disease. Bronchial artery embolization (BAE) has been established as one of the useful treatments of massive and persistent hemoptysis. We evaluated the efficacy and safety of BAE for controlling hemoptysis in MAC patients, and identified the risk factors of rebleeding after BAE. Methods Among the 529 patients with MAC who were admitted to our institution from January 2007 to December 2012, we retrospectively reviewed the demographic data, imaging, sputum, and angiographic findings, and the clinical course of 43 patients who underwent BAE using coils, due to hemoptysis. Results Among the 43 patients enrolled in the study, rebleeding developed in 13 cases (30.2%) with a mean follow-up period of 18 months. Median rebleeding-free time after BAE was 29.9 months and the cumulative hemoptysis control rates were 79.1%, 73.8%, and 63.3% in one, two, and three years, respectively. Rebleeding-free time significantly correlated with comorbid chronic pulmonary aspergillosis (CPA). When limited to 35 MAC patients without CPA, the rate increased to 88.6%, 82.1%, and 70.4%, respectively. Factors such as coexisting CPA, multiple embolized vessels at BAE, longer length of time from the diagnosis of MAC to BAE, and an administration of antibiotics for MAC at the time of hemoptysis, indicated statistically significant correlations with rebleeding. Major complications concerning BAE were not encountered. Conclusions BAE using coils is an effective and safe method for controlling hemoptysis in patients with MAC pulmonary disease. However, it is important to carefully observe patients with risk factors for rebleeding after BAE.

We occasionally experience cases suspected of pulmonary Mycobacterium avium complex (MAC) disease without positive bacterial cultures.To evaluate features of pulmonary MAC cases diagnosed later in the follow-up after negative intensive investigation.We defined and compared three groups; the first study negative (FSN) group, the first study positive (FSP) group, and MAC negative group. The FSN group consisted of patients negative for MAC isolation by bronchial washing performed between 2007 and 2011, but positive later. Patients with positive MAC cultures in the first study were incorporated into the FSP group. MAC negative group consisted of MAC suspects without MAC isolation in the follow-up.Twenty-four patients were classified as FSN group, 61 as MAC negative group and 265 as FSP group. FSN group exhibited more solitary nodule pattern (n = 7 in FSN, n = 6 in FSP; p0.001) and less nodular/bronchiectatic (NB) diseases (n = 17 in FSN, n = 245 in FSP; p0.001). When limited to NB type, the FSP group had more cavitations (6% in FSN, 32% in FSP; p = 0.028). Patients with more than three lung lobes involved were more frequent in the FSN group compared with FSP group with negative sputum cultures (65% vs 34%; p = 0.014) and with MAC negative group (65% vs 28%; p = 0.009).Patients diagnosed as pulmonary MAC disease in the follow-up duration tend to show solitary nodular pattern or NB pattern without cavitation. In FSN patients with NB pattern, more lung lobes were involved in the first study, suggesting subsequent MAC infection onto the underlying ectatic bronchi.