Underlying synovial sarcoma undiagnosed for more than 20 years in a patient with regional pain: a case report.

Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and relatively slow growth compared to other soft tissue sarcomas. Some patients with SS experience long-standing pain at the tumor site before the development of a palpable mass. Herein, we report the case of a 39-year-old woman with SS in the upper arm who presented with pain for > 20 years. The tumor detected on magnetic resonance imaging at 17 years was an SS. To the best of our knowledge, no English-language reports on imaging study-based identification of SS, which was undiagnosed for > 20 years, are known in the literature. This report discusses the imaging features of this latent lesion and the volume-doubling time of this unusual tumor.

Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306.

BACKGROUND: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS). METHODS: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS. RESULTS: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD. CONCLUSIONS: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk. CLINICAL TRIAL REGISTRATION: jRCTs031180003.

A randomized phase III trial of denosumab before curettage for giant cell tumor of bone. JCOG1610.

OBJECTIVES: The aim of JCOG1610 (randomized controlled phase III trial) was to confirm the superiority of preoperative denosumab to curettage with adjuvant local therapy for patients with giant cell tumor of bone without possible post-operative large bone defect. METHODS: The primary endpoint was relapse-free survival and the total sample size was set at 106 patients. Patient accrual began in October 2017. However, the accrual was terminated in December 2020 due to a recommendation from the Data and Safety Monitoring Committee because of poor patient accrual. Now, we report the descriptive results obtained in this study. RESULTS: A total of 18 patients had been registered from 13 Japanese institutions at the time of termination on December 2020. Eleven patients were assigned to Arm A (curettage and adjuvant local therapy) and 7 to Arm B (preoperative denosumab, curettage and adjuvant local therapy). Median follow-up period was 1.6 (range: 0.5-2.8) years. Protocol treatment was completed in all but one patient in Arm A who had a pathological fracture before surgery. All patients in Arm B were treated with five courses of preoperative denosumab. Relapse-free survival proportions in Arm A and B were 90.0% (95% confidence interval: 47.3-98.5) and 100% (100-100) at 1 year, and 60.0% (19.0-85.5) and 62.5% (14.2-89.3) at 2 years, respectively [hazard ratio (95% confidence interval): 1.51 (0.24-9.41)]. CONCLUSION: In terms of relapse-free survival, the superiority of preoperative denosumab was not observed in patients with giant cell tumor of bone without possible post-operative large bone defect.

Molecular characterization and secreted production of basidiomycetous cell-bound ß-glycosidases applicable to production of galactooligosaccharides.

Cell-bound ß-glycosidases of basidiomycetous yeasts show promise as biocatalysts in galactooligosaccharide (GOS) production. Using degenerated primers designed from Hamamotoa singularis (Hs) bglA gene, we newly identified three genes that encode cell-bound ß-glycosidase from Sirobasidium magnum (Sm), Rhodotorula minuta (Rm), and Sterigmatomyces elviae (Se). These three genes, also named bglA, encoded family 1 glycosyl hydrolases with molecular masses of 67‒77 kDa. The BglA enzymes were approximately 44% identical to the Hs-BglA enzyme and possessed a unique domain at the N-terminus comprising 110 or 210 amino acids. The Sm-, Rm-, and Se-BglA enzymes as well as the Hs-BglA enzyme were successfully produced by recombinant Aspergillus oryzae, and all enzymes were entirely secreted to the supernatants. Furthermore, addition of some nonionic detergents (e.g. 0.4% [v/v] Triton-X) increased the production, especially of the Hs- or Se-BglA enzyme. Out of the BglA enzymes, the Se-BglA enzyme showed remarkable thermostability (∼70°C). Additionally, the Sm- and Se-BglA enzymes had better GOS yields, so there was less residual lactose than in others. Accordingly, the basidiomycetous BglA enzymes produced by recombinant A. oryzae would be applicable to GOS production, and the Se-BglA enzyme appeared to be the most promising enzyme for industrial uses.

Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas.

The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

Evaluation of a silver-amplified immunochromatography kit for adenoviral conjunctivitis.

OBJECTIVE: To compare and evaluate the sensitivity of a newly developed silver-amplified immunochromatography (SAI) kit with various immunochromatography (IC) kits for adenoviruses based on the detection limit (copies/test). METHODS: An SAI kit and four ophthalmic IC kits were evaluated. The detection limits of the five kits were determined using the limiting dilution method for 15 conjunctivitis-associated adenoviruses (adenoviruses 1, 2, 3, 4, 5, 7, 8, 11, 37, 53, 54, 56, 64, 81, and 85). The detection limits were presented as numerical values as determined by real-time polymerase chain reaction (PCR). RESULTS: The detection limit of the SAI kit for the adenovirus types ranged from 1.0 × 103 -5.0 × 10 4 copies/test (geometric mean, 4.7 × 10 3 ). SAI had a 10-250-fold lower detection limit than the four IC kits for all adenoviruses studied. There were also differences in detection limits among the adenovirus types for each kit. DISCUSSION: The detection limit of the SAI kit was drastically reduced because the silver-amplification reaction increased the color development sensitivity. The results revealed the high sensitivity of SAI for detecting adenoviruses and suggested its usefulness for conjunctivitis examination.

Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG0304.

BACKGROUND: Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304. METHODS: Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m2 of DXR plus 10 g/m2 of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model. RESULTS: A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4-75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3-86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size. CONCLUSIONS: Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up. TRIAL REGISTRATION: This trial was registered at the UMIN Clinical Trials Registry as C000000096 on August 30, 2005.

Expression Profiling of Receptor-Activator of Nuclear Factor-Kappa B Ligand in Soft Tissue Tumors.

Bone and soft tissue tumors are derived from mesenchymal cells, and they are hard to treat. Receptor-activator of nuclear factor-kappa B ligand (RANKL) is an essential cytokine for osteoclast differentiation and activation and is expressed on the surface of osteoblasts or stromal cells. In this study, to explore the potential of denosumab treatment for soft tissue tumors, we analyzed the expression profiles of RANKL mRNA in 425 tumor specimens of 33 histological types by real-time RT-PCR. Denosumab is a monoclonal antibody that prevents the binding of RANKL to receptor-activator of nuclear factor-kappa B (RANK). For comparison, the relative expression levels of RANK and osteoprotegerin (OPG) mRNAs were also measured. OPG functions as a soluble decoy receptor for RANKL. Higher expression levels of RANKL mRNA were detected in calcifying aponeurotic fibroma, fibrosarcoma, calcifying epithelioma, myositis ossificans, heterotopic calcification, giant cell tumor of the tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS), compared with the levels of other tumor types. Moreover, the expression levels of RANK mRNA were highest in GCTTS, followed by myositis ossificans and PVNS, whereas the expression levels of OPG mRNA were greatly varied among these histological types. We then analyzed RANKL protein expression by immunohistochemistry in 57 tumor specimens with higher expression levels of RANKL mRNA. RANKL-positive cells were detected in GCTTS, PVNS, myositis ossificans, heterotopic calcification, and calcifying aponeurotic fibroma. In conclusion, RANKL is expressed in subsets of soft tissue tumors with calcification, and denosumab is a potential therapeutic option for soft tissue tumors expressing RANKL.

Prognostic impact of the tumor immune microenvironment in synovial sarcoma.

The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD-L1) were evaluated by immunohistochemistry. Moreover, we investigated PD-L1 and programmed death ligand 2 (PD-L2) mRNA expression in 19 of the 36 cases, using real-time PCR. The Kaplan-Meier method was used to estimate overall survival and progression-free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD-L1 expression was observed using immunohistochemistry. Moreover, although PD-L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression-free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD-L1, and PD-L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma.

Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304.

BACKGROUND: Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. METHODS: We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. RESULTS: Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. CONCLUSION: In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. METHODS: We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. RESULTS: Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2-41) and 6 (1-14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). CONCLUSION: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

Identification of genes involved in galactooligosaccharide utilization in Bifidobacterium breve strain YIT 4014T.

Galactooligosaccharides (GOS) are mixed oligosaccharides that are mainly composed of galactosyllactoses (GLs), which include 3'-GL, 4'-GL, and 6'-GL. Data from numerous in vitro and in vivo studies have shown that GOS selectively stimulate the growth of bifidobacteria. Previously, we identified the gene locus responsible for 4'-GL utilization, but the selective routes of uptake and catabolism of 3'- and 6'-GL remain to be elucidated. In this study, we used differential transcriptomics to identify the utilization pathways of these GLs within the Bifidobacterium breve YIT 4014T strain. We found that the BBBR_RS 2305-2320 gene locus, which includes a solute-binding protein (SBP) of an ATP-binding cassette (ABC) transporter and ß-galactosidase, were up-regulated during 3'- and 6'-GL utilization. The substrate specificities of these proteins were further investigated, revealing that ß-galactosidase hydrolyzed both 3'-GL and 6'-GL efficiently. Our surface plasmon resonance results indicated that the SBP bound strongly to 6'-GL, but bound less tightly to 3'-GL. Therefore, we looked for the other SBPs for 3'-GL and found that the BBBR_RS08090 SBP may participate in 3'-GL transportation. We also investigated the distribution of these genes in 17 bifidobacterial strains, including 9 B. breve strains, and found that the ß-galactosidase genes were present in most bifidobacteria. Homologues of two ABC transporter SBP genes were found in all B. breve strains and in some bifidobacteria that are commonly present in the human gut microbiota. These results provide insights into the ability of human-resident bifidobacteria to utilize the main component of GOS in the gastrointestinal tract.

Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group.

BACKGROUND: Pathological fracture of the proximal femur is a main cause of cancer patients losing their ability to walk. Although both osteosynthetic devices (predominantly intramedullary nails) and prosthetic replacement have been widely performed for treatment, controversies exist regarding which procedure should be used for the various conditions. In order to decide the eligibility criteria of a planned randomized prospective study about the treatment of pathological fractures of the proximal femur, we assessed the factors affecting the selection of operative procedures using questionnaires sent to the members of the Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG). METHODS: Questionnaire surveys to evaluate (1) the priority levels of the factors, (2) the equipoise range of each factor in situations where either procedure could be applied, (3) risk and benefit of each procedure, and (4) the degree of bone destruction affecting the selection of operative procedures, were sent to 26 institutions. RESULTS: Over 80% of the institutions answered. Orthopaedic surgeons of BSTTSG decided on the procedure according to the following factors in descending order: life expectancy, performance status before fracture, the degree of bone destruction, walking ability before fracture, general complications, the number of bone metastases in other sites, and the visceral metastasis status. With regard to bone destruction, (1) the involvement of the head, neck, calcar, and intertrochanteric region, (2) transverse destruction >1/2, and (3) soft-tissue tumor extension, were the factors that led to the choice of prosthesis treatment. CONCLUSIONS: Using these identified factors, the inclusion criteria for the prospective randomized study of the surgical treatment of metastatic bone tumors of the proximal femur were optimized. The evaluation system about the bone destruction of metastases needs to be refined through the following prospective randomized study.

Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients.

BACKGROUND: Bone and soft tissue sarcomas (BSTS) are rare malignant tumors. Recently, the combination of gemcitabine and docetaxel (GD) was shown to have activity as second-line setting in BSTS. However, the efficacy as first-line and adjuvant settings and precise profiles of adverse events in Japanese patients are not known yet. In the present study, the feasibility and efficacy of GD in patients with BSTS were investigated. METHODS: Patients with BSTS treated with GD in our institutions were retrospectively analyzed. Information regarding clinical features, adverse events, and outcome was collected and statistically studied. Factors related to survival were analyzed using log-rank test and Cox proportional hazard regression method. RESULTS: A total of 134 patients were analyzed. GD was carried out as adjuvant setting in 9, first-line in 23, second-line in 56, and third-or-greater line in 46 patients. The response rate (RR) for all patients was 9.7%. RR for the patients treated as adjuvant or first-line setting was 18.8%, whereas that as second-or-greater line was 6.9%. The median progression-free survival (PFS) and overall survival (OS) of all patients were 4.8 (95% CI 3.5-6.1) and 16.4 (95% CI 9.8-22.9) months, respectively. Survival tended to be better in the patients treated as first-line than in those treated as second-or-greater line. Multivariate analysis demonstrated that history of prior chemotherapy (p = 0.046) and response to GD (p = 0.009) was significantly associated with PFS and OS, respectively. The leucopenia and neutropenia were the most frequent adverse events, and grade 3 or 4 leucopenia and neutropenia were observed in 69.4 and 72.4% of the patients. Grade 2 or 3 pneumonitis was observed in one (0.7%) and four (3.0%) patients, respectively. All the patients with pneumonitis had experienced prior chemotherapy and/or radiotherapy. CONCLUSIONS: GD used as both first- and second/later line is effective chemotherapy for a proportion of patients with advanced BSTS. Higher response rate and better outcome was achieved in chemotherapy-naïve patients. This regimen is associated with high incidence of severe hematological toxicity, as well as the risk of severe pneumonitis, especially in pre-treated patients. GD is promising for further analysis by phase III study for the patients with BSTS.

Intravertebral cleft in pathological vertebral collapse resulting from cancer metastasis: report of three cases.

Intravertebral cleft (IVC) is a common finding in osteoporotic compression fracture. However, since the vertebral collapse attributable to cancer metastasis is rarely associated with IVC, the phenomenon is generally considered as a sign of a benign lesion. In this study, we retrospectively reviewed the radiographs, computed tomography scans, and magnetic resonance images of 111 patients with spinal metastasis. Three cases (2.7 %) had IVC in the collapsed thoracic vertebral bodies (T7, T8, and T11) attributable to cancer metastasis. IVC alone is not necessarily an indicator of a benign vertebral collapse.

[Multicenter Prospective Observational Study of Fungal Keratitis--Identification and Susceptibility Test of Fungi].

PURPOSE: To investigate the causative fungi of fungal keratitis in Japan and their drug susceptibility. METHODS: Identification and antifungal susceptibility test for 8 drugs (micafungin, amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, miconazole and pimaricin) were performed using isolated fungi from patients with fungal keratitis treated at 27 facilities in Japan between November 1, 2011 and October 31, 2013. RESULTS: Fungal strains were detected in 72 (50.7%) out of 142 samples. The major isolates were Fusarium spp. (18), Candida parapsilosis (12), C. albicans (11) and Alternaria spp. (6), in all, fungi of 31 species were identified by gene analysis. In the yeast-like fungi, susceptibility rates were evident for more than 80% in voriconazole, pimaricin, flucytosine, micafungin, amphotericin B and fluconazole. In filamentous fungi, the susceptibility rate was less than 50% except for PMR (90%). Fusarium spp., which were susceptible to amphotericin B and pimaricin, showed lower susceptibility rates compared with other genera. CONCLUSIONS: Although various genera and species of fungi cause fungal keratitis, the obtained drug susceptibility data in this study demonstrates the different susceptibility patterns among the major isolates (Fusarium spp., C. parapsilosis, C. albicans and other groups). This is important evidence useful for fungal keratitis treatment.

[Multicenter Prospective Observational Study of Fungal Keratitis--Current Status of Patients' Background, Clinical Findings, Treatment and Prognosis].

PURPOSE: To investigate the current status of fungal keratitis in Japan. METHODS: The patients with fungal keratitis were examined at 27 facilities in Japan from November 1st 2011 to October 31st 2013, concerning isolates, patient background, clinical findings, treatment and prognosis. RESULTS: Out of 139 cases, 133 were diagnosed as fungal keratitis, of which fungi were isolated from 72 samples of 71 cases (yeast-like fungi 32 strains and filamentous fungi 40 strains). The corrected visual acuity at the first visit of 88 cases (66.2%) was less than 20/200 and 42 cases (31.6%) were involved with deep stromal lesions, indicating high proportion of severe cases in this study. Three months later, 56 cases (42.1%) were still under treatment, and corrected visual acuity of 57 cases (42.9%) was less than 20/200. In cases with yeast-like fungi, there were significantly more cases with past history of corneal diseases, ocular surgery including keratoplasty, and eye drops' use such as steroids than those with filamentous fungi. On the other hand, there were significantly more cases of filamentous fungi, with trauma on the onset and with intervention of previously attending doctors than those with yeast-like fungi. Logistic regression analyses revealed that contact lens wearing was a significant factor of good prognosis, and yeast-like fungi as one of poor outcome compared with no fungal isolation. CONCLUSION: Although the choice of antifungal drugs has been increasing, fungal keratitis is still severe, refractory and vision-threatening disease.

Perioperative chemotherapy with ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities (JCOG0304).

OBJECTIVE: The efficacy of perioperative chemotherapy for soft tissue sarcomas is controversial and only a few prospective studies of pre-operative chemotherapy for soft tissue sarcomas in the extremities have been reported. We therefore carried out Phase II study of perioperative chemotherapy for patients with soft tissue sarcomas in the extremities. METHODS: Patients with Stage III non-round cell soft tissue sarcomas in the extremities were eligible. The patients were treated with pre-operative chemotherapy consisting doxorubicin 60 mg/m(2) and ifosfamide 10 g/m(2) for three courses. After the tumor resection, two additional courses of the same regimen were carried out. RESULTS: A total of 72 patients were enrolled and 70 patients were eligible. The median age of the patients was 49 years. The major pathological subtypes were synovial sarcoma in 20 and undifferentiated pleomorphic sarcoma in 17 patients. The protocol treatments were completed in 74% of the eligible cases. The 2 and 5-year progression-free survival rates were 75.7% (95% CI, 63.9-84.1%) and 63.8% (95% CI, 51.3-73.9%), respectively. The 5-year overall survival was 82.6% (95% CI, 71.3-89.7%). There was no treatment-related death. Grade 3 or 4 hematological toxicities (leukopenia and neutropenia) were observed in most of the patients. CONCLUSIONS: Although the toxicities of the regimen were significant, pre-operative chemotherapy followed by post-operative chemotherapy using doxorubicin and high-dose ifosfamide was feasible. The outcome of the trial for the patients with high-grade soft tissue sarcomas in the extremities was favorable, and this regimen is promising for further investigation. This trial was registered at the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) as C000000096.

Diverse galactooligosaccharides consumption by bifidobacteria: implications of ß-galactosidase--LacS operon.

Galactooligosaccharides (GOS) possess prebiotic properties that specifically increase the number of bifidobacteria in the human intestine, thus giving health benefits to the host. Although the bifidogenic effect of GOS has been demonstrated in numerous studies, the utilization of GOS by specific bifidobacteria remains unclear. The goal of our study was to elucidate GOS consumption by specific bifidobacteria and gain insights into the mechanism. First, we examined GOS consumption by 14 bifidobacterial strains belonging to seven different species by comparing growth rate, carbohydrate consumption, and acid production. We then performed a transcription analysis in the case of one strong GOS consumer, Bifidobacterium adolescentis YIT 4011(T), to predict the operon contributing to GOS use. The study indicated the contribution of an operon consisted of LacS symporter and ß-galactosidase to bifidobacterial GOS consumption.

[Antimicrobial Effects of Iodine-Polyvinyl Alcohol Ophthalmic and Eye Washing Solution (PA * IODO) with Special Reference to its Temperature, Concentration and Time and its Preservation Stability].

PURPOSE: Temperature, concentration and time are the three factors that affect the inactivation capacity of iodine antiseptics. We investigated the effect of these factors on the microbe inactivation of Iodine-Polyvinyl Alcohol ophthalmic and eye washing solution (PA * IODO), and also investigated the preservation conditions on stability of the inactivation activity of the PA * IODO. METHODS: Test microbes were mixed with PA * IODO, varying the three factors. The live microbes were counted after each reaction. The effects of plugging and preservation temperature were investigated to determine the preserving stability. RESULTS: The inactivation capacity of PA * IODO tended to decrease in almost all microbes tested at 4 degrees C. Twenty times or less diluted PA * IODO killed almost all microbes completely. The time effect was more marked in viruses. Plugging and low-temperature made iodine concentration in diluted PA * IODO remain relatively high. CONCLUSIONS: The concentration of PA * IODO affected the inactivation ability more than the temperature and time, although all the three factors correlated positively to the inactivation. For preservation the diluted PA * IODO needed plugging and low temperature.