[Mullerian Cyst in the Posterior Mediastinum Resected by Robot-assisted Thoracic Surgery:Report of a Case].

Mullerian cyst in the posterior mediastinum is a rare disorder. We report on the case of a woman in her 40s with a cystic nodule which is located in the right posterior mediastinum next to the vertebra at the level of tracheal bifurcation. The tumor was suggested to be cystic by preoperative magnetic resonance imaging (MRI). The tumor was resected with robot-assisted thoracic surgery. Pathology by hematoxylin-and-eosin (H&E) revealed a thin-walled cyst lined by ciliated epithelium without cellular atypia. The diagnosis of Mullerian cyst was confirmed by immunohistochemical staining which showed the positive findings for estrogen receptor (ER) and progesterone receptor of the lining cells.

Outcomes of adult patients with early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) and non-ETP T-ALL.

Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL) is generally considered to be a high-risk subtype. We retrospectively analyzed the clinical outcomes of adult patients diagnosed with ETP-ALL or other T-cell ALL (non-ETP T-ALL). The subjects were 82 patients (ETP-ALL: n = 18, non-ETP T-ALL: n = 64) for whom relevant immunophenotype data needed for classification were available. ETP-ALL patients were older (median age, 50.5 vs. 33.5 years, P = 0.042) and had less mediastinal involvement (27.8 vs. 73.4%, P < 0.001). The rate of complete remission (CR) with the first induction therapy was significantly lower in the ETP group (33.3 vs. 64.0%, P = 0.03), but the CR rate within 2 cycles of chemotherapy did not differ significantly (61.1 vs. 76.6%, P = 0.232). The 3-year overall survival (OS) rate was also similar in both groups (43.2 vs. 45.8%, P = 0.992). The ETP phenotype had no impact on survival in the transplant group or the non-transplant group. A multivariate analysis identified the male sex as a poor prognostic factor (HR: 4.43, P < 0.01), but not the immunophenotype of ETP. The prognosis for adult patients with ETP-ALL was comparable to that of non-ETP T-ALL patients. However, further studies aimed at improving the remission rate for ETP-ALL are needed.

Good recovery without decompression fasciotomy for crush syndrome caused by using a Japanese-style toilet.

We report a case of crush syndrome that developed while the patient was squatting to use a Japanese-style toilet. The patient was a 61-year-old male with an obese body. He was sitting on the toilet and couldn't stand up, and after a few hours, the landlord found him and called the emergency services. On presentation, the patient was hyperkalemic and in shock, and his serum creatine kinase levels rose to a maximum of 287,600 U/L. He was diagnosed with postural crush syndrome in both lower extremities due to squatting position in a Japanese-style toilet. Subjective symptoms, physical examination, and blood tests were monitored and the patient was observed. As a result, the patient could be treated conservatively without fasciotomy. Dialysis was not necessary because the fluid infusion maintained adequate urine output and corrected the hyperkalemia. Magnetic resonance imaging of both lower extremities showed multiple high-signal areas in the muscles of the bilateral thighs and lower legs. This case suggested that if the wound is closed, the peripheral pulse is palpable, and the patient's symptoms have improved, a fasciotomy should not be performed. People who are too heavy to squat may need to be careful when using this kind of toilet.

The incidence of toxic shock syndrome due to nosocomial methicillin-resistant Staphylococcus aureus infection in burn patients: A four-year retrospective cohort study.

Among adult and pediatric patients, concern is growing in regard to toxic shock syndrome (TSS) resulting from methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infection. We investigated the incidence and characteristics of this form of TSS in patients with burn injury who were admitted to our burn care units from January 2008 to December 2011. Of the 244 patients with nosocomial MRSA infection admitted during the study period, TSS occurred in 20 (8.2%) patients whose average age was 42.9 years, average total burn surface area (TBSA) was 31.7%, and average day of TSS appearance was 9.5 days after injury. There were no particular characteristics associated with age, TBSA or day of TSS appearance in these patients. All but 1 patient recovered from TSS within an average of 9.4 days. The incidence of TSS due to nosocomial MRSA infection in these burn patients was higher than expected. TSS due to nosocomial MRSA infection should be considered in burn care.

Low-dose lenalidomide and dexamethasone therapy after melphalan-prednisolone induction in elderly patients with newly diagnosed multiple myeloma.

Lenalidomide (Len) and dexamethasone (dex) therapy is a standard therapy in patients with multiple myeloma. Elderly or unfit patients may reduce Len or dex doses to prevent toxicities that lead to treatment discontinuation. However, there have been few studies evaluating the efficacy and safety of lower doses of Len and dex. We conducted a phase II study of 1.5-year low-dose Len and dex therapy following melphalan and prednisolone (MP), the number of which cycles was determined by a response within 9 cycles. The Len dose was 10 mg daily and the dex dose was 20 mg weekly, which were continued for 1.5 years. Twenty-one patients were enrolled. The median number of cycles of MP was 3 (range, 2-9). The overall response rate was 81% and a very good partial response or better was achieved in 33.3% of patients. The median follow-up time for survivors was 70.5 months (range, 42-83 months), the median progression-free survival (PFS) was 27 months (95% CI, 21-33 months), and the median overall survival was not reached. Grade 3 or 4 adverse events were observed in 28.6% of patients. In conclusion, the low-dose Len and dex therapy safely achieved comparable efficacies to the standard-dose regimen in elderly patients with newly diagnosed multiple myeloma. UMIN000007889.

Rapidly progressive renal failure due to tubulointerstitial infiltration of peripheral T-cell lymphoma, not otherwise specified accompanied by uveitis: a case report.

BACKGROUND: Rapid decline in renal dysfunction due to primary renal lymphoma, or secondary renal lymphoma by infiltration from a primary origin, is extremely rare. There are notably few reports indicating infiltration of T-cell lymphoma into the kidney. CASE PRESENTATION: A 61-year-old woman with a sudden body rash and liver dysfunction was brought to our hospital presenting with a dull headache and blurred vision. Laboratory tests revealed rapidly progressive renal failure. Histological examination of the kidney and skin indicated infiltration of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Infiltration of PTCL-NOS to the liver and spleen, and presence of Uveitis masquerade syndrome were suspected. Imaging showed that the lesion was limited to extralymphatic organs. Renal function was improved with administration of steroids, including pulse steroid therapy, before administering cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. CONCLUSIONS: This is the first reported case of rapidly progressive renal failure caused by perivascular tubulointerstitial nephritis with the direct invasion of PTCL-NOS. In our case, a single steroid dose showed dramatic results with respect to renal symptoms.

Cerebellar ataxia-dominant phenotype in patients with ERCC4 mutations.

Autosomal recessive cerebellar ataxias (ARCAs) are clinically and genetically heterogeneous neurological disorders. Through whole-exome sequencing of Japanese ARCA patients, we identified three index patients from unrelated families who had biallelic mutations in ERCC4. ERCC4 mutations have been known to cause xeroderma pigmentosum complementation group F (XP-F), Cockayne syndrome, and Fanconi anemia phenotypes. All of the patients described here showed very slowly progressive cerebellar ataxia and cognitive decline with choreiform involuntary movement, with young adolescent or midlife onset. Brain MRI demonstrated atrophy that included the cerebellum and brainstem. Of note, cutaneous symptoms were very mild: there was normal to very mild pigmentation of exposed skin areas and/or an equivocal history of pathological sunburn. However, an unscheduled DNA synthesis assay of fibroblasts from the patient revealed impairment of nucleotide excision repair. A similar phenotype was very recently recognized through genetic analysis of Caucasian cerebellar ataxia patients. Our results confirm that biallelic ERCC4 mutations cause a cerebellar ataxia-dominant phenotype with mild cutaneous symptoms, possibly accounting for a high proportion of the genetic causes of ARCA in Japan, where XP-F is prevalent.

An Lysophosphatidic Acid Receptors 1 and 3 Axis Governs Cellular Senescence of Mesenchymal Stromal Cells and Promotes Growth and Vascularization of Multiple Myeloma.

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells and there is much interest in how MSCs contribute to the regulation of the tumor microenvironment. Whether MSCs exert a supportive or suppressive effect on tumor progression is still controversial, but is likely dependent on a variety of factors that are tumor-type dependent. Multiple myeloma (MM) is characterized by growth of malignant plasma cells in the bone marrow. It has been shown that the progression of MM is governed by MSCs, which act as a stroma of the myeloma cells. Although stroma is created via mutual communication between myeloma cells and MSCs, the mechanism is poorly understood. Here we explored the role of lysophosphatidic acid (LPA) signaling in cellular events where MSCs were converted into either MM-supportive or MM-suppressive stroma. We found that myeloma cells stimulate MSCs to produce autotaxin, an indispensable enzyme for the biosynthesis of LPA, and LPA receptor 1 (LPA1) and 3 (LPA3) transduce opposite signals to MSCs to determine the fate of MSCs. LPA3-silenced MSCs (siLPA3-MSCs) exhibited cellular senescence-related phenotypes in vitro, and significantly promoted progression of MM and tumor-related angiogenesis in vivo. In contrast, siLPA1-MSCs showed resistance to cellular senescence in vitro, and efficiently delayed progression of MM and tumor-related angiogenesis in vivo. Consistently, anti-MM effects obtained by LPA1-silencing in MSCs were completely reproduced by systemic administration of Ki6425, an LPA1 antagonist. Collectively, our results indicate that LPA signaling determines the fate of MSCs and has potential as a therapeutic target in MM. Stem Cells 2017;35:739-753.

Low Level of TSST-1 Antibody in Burn Patients With Toxic Shock Syndrome Caused by Methicillin-Resistant Staphylococcus aureus.

Toxic shock syndrome (TSS) caused by methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infection is a growing concern in both adult and pediatric patients. The reason why TSS appears in only some patients with MRSA infection remains unclear. In this study, we analyzed serial TSS toxin-1 (TSST-1) antibody in patients with burn injury to investigate the mechanisms of TSS caused by MRSA nosocomial infection. This study comprised of patients with burn injury in our burn care unit from September, 2010 to August, 2011. Serum samples were collected serially on admission, at 48 to 72 hours after injury, on the day MRSA infection appeared, and on the day MRSA infection resolved. TSST-1 antibody was measured by enzyme-linked immunosorbent assay (ELISA). TSS was diagnosed according to the criteria of the Centers for Disease Control. Serial serum samples were collected from 24 patients and nosocomial MRSA infection was detected in 12 patients. In these 12 patients, TSS occurred in five patients (TSS+ group) but did not occur in the other seven patients (TSS- group). TSST-1 antibody level was significantly lower in the TSS+ group than TSS- group on admission and on the day MRSA infection appeared. All patients in the TSS+ group received intravenous immune globulin when TSS was diagnosed, and no patients died of TSS. Patients suffering from TSS had a lower level of TSST-1 antibody than patients not suffering from TSS. Testing for TSST-1 antibody in the clinical setting might help to predict and prevent the appearance of TSS caused by nosocomial MRSA infection.

GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells.

The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells. However, the molecular mechanism of bone marrow mesenchymal stem cell differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cell function as well as other hematopoietic lineages, suggesting that it may maintain bone marrow mesenchymal stem cells in an immature state and also contribute to their differentiation. To explore this possibility, we established bone marrow mesenchymal stem cells from GATA2 conditional knockout mice. Differentiation of GATA2-deficient bone marrow mesenchymal stem cells into adipocytes induced accelerated oil-drop formation. Further, GATA2 loss- and gain-of-function analyses based on human bone marrow mesenchymal stem cells confirmed that decreased and increased GATA2 expression accelerated and suppressed bone marrow mesenchymal stem cell differentiation to adipocytes, respectively. Microarray analysis of GATA2 knockdowned human bone marrow mesenchymal stem cells revealed that 90 and 189 genes were upregulated or downregulated by a factor of 2, respectively. Moreover, gene ontology analysis revealed significant enrichment of genes involved in cell cycle regulation, and the number of G1/G0 cells increased after GATA2 knockdown. Concomitantly, cell proliferation was decreased by GATA2 knockdown. When GATA2 knockdowned bone marrow mesenchymal stem cells as well as adipocytes were cocultured with CD34-positive cells, hematopoietic stem cell frequency and colony formation decreased. We confirmed the existence of pathological signals that decrease and increase hematopoietic cell and adipocyte numbers, respectively, characteristic of aplastic anemia, and that suppress GATA2 expression in hematopoietic stem cells and bone marrow mesenchymal stem cells.

Induction of thymic stromal lymphopoietin in mesenchymal stem cells by interaction with myeloma cells.

Recently, the bone marrow (BM) microenvironment has been reported to support the survival of multiple myeloma (MM) cells. In this study, we examined changes in gene expression profile in human mesenchymal stem cells (MSCs) by co-culture with MM cells. cDNA array analysis indicated that co-culture induced multiple factors which have positive effects on the survival of MM cells, such as interleukin-6 (IL-6) and insulin-like growth factor-1. Other than these factors, thymic stromal lymphopoietin (TSLP), which is a cytokine involved in the progression of pancreatic and breast cancer through induction of T helper 2 cell responses, was up-regulated in MSCs. TSLP exhibited no effect on proliferation or drug resistance of MM cells, but TSLP secreted from MSCs by co-culture expanded IL-13+ CD4+ T cells through stimulation of dendritic cells. These results suggested that MM cells positively act to induce various molecules in MSCs, leading to the formation of a more advantageous BM microenvironment for their survival.

Successful allogeneic hematopoietic stem cell transplantation for aggressive NK cell leukemia.

Aggressive natural killer cell leukemia (ANKL) is a highly aggressive lymphoproliferative disease. An appropriate therapeutic strategy for ANKL remains to be established, but a few case reports have suggested that allogeneic hematopoietic stem cell transplantation (allo-HCT) can be curative. Here, we report a young woman with ANKL showing central nervous system (CNS) invasion, who has been in complete remission for more than a year after allo-HCT following two courses of intravenous chemotherapy and several rounds of intrathecal chemotherapy. Intensive remission induction chemotherapy followed by conventional myeloablative allo-HCT is a promising approach for long-term remission in cases of this aggressive malignancy.

Acquired hemophilia A with sigmoid colon cancer: successful treatment with rituximab followed by sigmoidectomy.

Acquired hemophilia A is a rare and potentially fatal condition of coagulopathy caused by autoantibodies against clotting factor VIII (factor VIII inhibitor). We report a case of a 63-year-old woman, who presented with a sudden onset of severe hemorrhagic tendency with exclusively prolonged activated partial thromboplastin time (APTT). She was diagnosed with acquired hemophilia A due to a decrease in factor VIII activity and a high titer of factor VIII inhibitor. Hemorrhage was well controlled by recombinant activated factor VII. Although the level of factor VIII inhibitor did not decline with prednisolone and cyclophosphamide, it became undetectable with rituximab. In parallel with controlling hemorrhage, malignancy, which may cause acquired hemophilia A, was searched for and sigmoid colon cancer was found. After the eradication of factor VIII inhibitor, surgical resection was performed uneventfully. Thereafter, acquired hemophilia A has been in complete remission without any additional therapy. The present case suggests the efficacy of rituximab for refractory acquired hemophilia A and the importance of the identification of underlying diseases that can cause acquired hemophilia A.