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Endocrine dysfunction can considerably impact the nervous system. Various nonspecific neurological symptoms can manifest, including headache, muscle weakness, involuntary movements, and impaired consciousness. Because of their lack of specificity, endocrine abnormalities underlying neurological symptoms may not be recognized and making the diagnosis may be challenging. It is essential that clinicians not overlook endocrine disorders when diagnosing neurological symptoms, as prompt and appropriate treatment, such as hormone replacement therapy, can improve a patient's general condition and neurological symptoms.

A 61-year-old woman was referred for further evaluation of an intracystic nodule in her left upper lung. Computed tomography( CT) showed a 15 mm nodule in a pulmonary cyst adjacent to aortic arch and mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET)-CT showed little uptake of FDG in the lesion. No abnormality was found in the bronchoscopy findings. On imaging findings, the possibility of pulmonary aspergilloma was considered, but the serological findings were inconsistent, and surgical resection of the lesion was performed for both diagnosis and treatment. The final pathohistological diagnosis was well differentiated liposarcoma. No adjuvant therapy was performed and the patient has been well without recurrence for 2 years after the surgery. We report a rare case of well differentiated liposarcoma of a lung mimicking pulmonary aspergilloma.

Acute myeloid leukemia (AML) is one of the most common hematologic malignancies derived from self-renewing and highly propagating leukemic stem cells (LSCs). We have previously identified T-cell immunoglobulin mucin-3 (TIM-3) as an AML LSC-specific surface molecule by comparing the gene expression profiles of LSCs and hematopoietic stem cells (HSCs). TIM-3 expression clearly discriminates LSCs from HSCs within the CD34 + CD38 - stem cell fraction. Furthermore, AML cells secrete galectin-9 (Gal-9, a TIM-3 ligand) in an autocrine manner, resulting in constitutive TIM-3 signaling, which maintains LSC self-renewal capacity through β-catenin accumulation. In this study, we investigated the LSC-specific mechanisms of TIM-3 signaling. We found that TIM-3 signaling drove the canonical Wnt pathway, which was independent of Wnt ligands, to maintain cancer stemness in LSCs. Gal-9 ligation activated the cytoplasmic Src homology 2 (SH2) binding domain of TIM-3 to recruit hematopoietic cell kinase (HCK), a Src family kinase that is highly expressed in LSCs. HCK phosphorylated p120-catenin to promote the formation of the LDL receptor-related protein 6 (LRP6) signalosome, hijacking the canonical Wnt pathway. This TIM-3/HCK/p120-catenin axis was employed principally in immature LSCs compared to TIM-3-expressing exhausted T-cells.

A quinquagenarian woman visited our hospital due to experiencing headache around the right upper eyelid for the previous 2 months. T 2 -weighted MRI of the head showed multiple high-signal-intensity lesions in the corpus callosum and bilateral corona radiata. She was thought to have an autoimmune disease and was treated with steroid pulse therapy, but the light reflex of the right eye diminished and the patient developed inferior horizontal hemianopsia. T 2 -weighted orbital MRI showed an enlarged right optic nerve, a high-intensity signal in the superior half of the optic nerve, and an enhancing effect. She also tested positive for anti-aquaporin 4 antibodies, so she was diagnosed with neuromyelitis optica spectrum disorder (NMOSD). This case shows that headache can be an initial symptom of NMOSD and that clinicians should consider NMOSD when attempting to diagnose patients presenting with headaches.

Genomics and novel molecularly targeted drugs for treating acute myelogenous leukemia (AML) are developing rapidly. To optimize the allocation of patients to the best possible treatment, we have to expedite test results of cytogenetic and molecular analyses for target mutations such as CBF and FLT3, since gene mutations are specifically associated with patient prognosis and therefore inform medical decision making. However, novel agents cannot completely eradicate AML because of the emergence of resistance to these agents; therefore, at the moment it is still necessary to combine cytotoxic treatment with novel agents. Hence, it becomes vital to understand how to stratify AML patients and subsequently treat the right patients with the right combination of cytotoxic treatments and novel agents.

Despite recent progress in diagnosis and leukemogenesis based on genomic landscapes in acute myelogenous leukemia (AML), advances in AML treatment lag behind. Over the past four decades, combination chemotherapy with anthracycline and cytarabine remains the standard induction therapy. Subsequent post-remission consolidation therapy stratifies patients into favorable-risk, intermediate-risk, and unfavorable-risk groups to assign post-remission therapies based on cytogenetic abnormalities and molecular mutations. Allogeneic stem-cell transplant decreases the risk of AML recurrence compared to standard chemotherapy, but it also raises the risk of serious complications. Recent large collections of matched genomic and clinical data may assist in selecting the best individualized therapy for each AML patient. Emerging evidence indicates that molecularly targeted therapies such as FLT3 and IDH inhibitors may be effective in distinct AML subtypes, providing further rationale for a personalized medicine approach. An umbrella trial, such as "BEAT AML Master Trial," designed to offer novel targeted therapy to AML patients based on their genetic characteristics, will be launching worldwide in the near future.

Hematopoietic stem cells (HSCs) have the potential to self-renew and differentiate into multi-lineage mature hematopoietic cells; thus, these cells can maintain hematopoiesis. Human HSCs reside within the CD34 + CD38 - cell fractions. Similarly, in acute myelogenous leukemia (AML), a small number of leukemic cells, called leukemic stem cells (LSCs), can be enriched within the identical CD34 + CD38 - cell fractions. LSCs can self-renew and produce clonogenic leukemic cells, whereas non-LSCs lack the potential to self-renew or maintain leukemia; thus, AML is organized as a hierarchy that originated from LSCs. LSCs play a central role in the maintenance and progression of leukemia; therefore, these cells should be an ultimate target for the eradication of human AML. Previous studies have revealed specific molecular machineries essential for LSCs. Targeting LSC-specific molecules should be a good therapeutic approach to kill LSCs without affecting normal cells. In this review, we would like to introduce the recent progress in the LSC study.

Acute myeloid leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. We previously reported that the T-cell immunoglobulin mucin-3 (TIM-3) is expressed on the LCS surface in most types of AML. Since only the TIM-3(+), i.e. not the TIM-3(-), fraction of human AML cells can reconstitute human AML in immunodeficient mice, we hypothesized that the TIM-3 has an essential function in maintaining AML LSCs. Herein, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for human AML LSC development. Serum Gal-9 was significantly elevated in primary AML patients and in mice xenografted with human AML. Neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML, as well as Gal-9 ligation of TIM-3 co-activated NF-κB and β-catenin signaling, suggesting that TIM-3 signaling is necessary for LSC self-renewal. Interestingly, identical changes were found to be involved in the progressive transformation of a variety of pre-leukemic disorders into myeloid leukemia. Thus, molecules constituting the TIM-3/Gal-9 autocrine loop are potential therapeutic targets applicable to most types of myeloid leukemia.

Acute myelogenous leukemia (AML) originates from self-renewing leukemic stem cells (LSCs), an ultimate therapeutic target for AML. LSCs play a central role in the propagation of leukemia through their unique stem cell like properties, and LSCs share the many functional molecules with their normal counterpart hematopoietic stem cells (HSCs). For the establishment of LSCs-specific therapeutic approaches, it is quite important to understand the biological differences between LSCs and HSCs. Recent, studies have succeeded in clarifying these biological differences. In this review, I would like to introduce the biological significance of LSCs and discuss the molecular targeted therapy against LSCs.

Radiotherapy has been regularly applied mainly for inoperable patients with non- small cell lung cancer, and various clinical trials have been performed. On the other hand, we have applied percutaneous cryoablation for lung tumors (PCLT) since 2002. In this paper, we describe our experience of PCLT compared to the results of radiation treatment. Three-year local progression-free rates with stereotactic body radiotherapy were 79-92% in stage I A and 30-79% in stage I B. Those with proton radiotherapy were 82-89% in stage I A and 49-62% in stage I B. CTCAE grade ≥3 complications occurred in 3-28% cases, such as radiation pneumonitis. As for PCLT, 1-, 2- and 3-year local progression-free rates were 80.4%, 69.0% and 67.7%, respectively. Pneumothorax, pleural effusion, and hemoptysis occurred after 61.7%, 70.5%, and 36.8% sessions, respectively. Of all cases with pneumothorax, 17.6% required chest tube insertion and 1.7% required pleurodesis. Delayed and recurrent pneumothorax occurred in 7.8% each. CTCAE grade ≥3 complications occurred in 1.5% cases. The biggest advantage of PCLT compared with radiotherapy is the possibility to treat local recurrence at the same site as treated before. In addition, no radiation pneumonitis occurs in PCLT. Moreover, less space or budget is needed when PCLT is newly introduced in a hospital. Although high reliable clinical data is not achieved yet, PCLT is one of the promising methods in local treatment.

Reactive oxygen species (ROS) derived from mitochondria play an essential role in stroke as well as in neurodegenerative disorders. Although hyperglycemia associated with diabetes mellitus is well known to enhance ROS production in vascular endothelial cells, the effects of either acute or chronic high glucose environments on neurons and glial cells remain unclear. Astroglia play a pivotal role in glucose metabolism. Thus, the astroglial metabolic response to high glucose environments is an interesting subject. In particular, the glutathione/pentose phosphate pathway (PPP) system, which is a major defense mechanism against ROS in the brain, contributes to glucose metabolism and is more active in astroglia. We propose that high glucose environments activate PPP through an increased flux to the hexosamine biosynthetic pathway (HBP). HBP is known to induce endoplasmic reticulum (ER) stress under hyperglycemia, resulting in the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2), a master regulator of phase 2 detoxifying enzymes including glucose-6-phosphate dehydrogenase that regulates PPP activity, as Nrf2 is reported to be a direct substrate of protein kinase RNA (PKR)-like ER kinase (PERK), a transducer of ER stress. Therefore, the phosphorylation of Nrf2 by hyperglycemia-induced ER stress facilitates Nrf2 translocation through PERK, thus activating the PPP. If acute or chronic hyperglycemia induces PPP activation in astroglia to reduce ROS, reducing the glucose concentration may be accompanied by a risk, which may explain the lack of evidence that strict glycemic control during the acute phase of stroke conveys no beneficial effect.

Case 1 was a 73-year-old woman admitted to our hospital due to bilateral pneumonia with respiratory failure. Real-time reverse transcription polymerase chain reaction (RRT-PCR) analysis confirmed 2009 H1N1 influenza infection. Streptococcus pneumoniae was confirmed from sputum culture and a urine antigen test on admission. She was treated with antiviral drugs and antibiotics, and improved gradually. Case 2 was a 66-year-old woman admitted to our hospital due to suspected acute exacerbation of interstitial pneumonitis. RRT-PCR analysis confirmed 2009 H1N1 influenza infection, and methicillin-resistant Staphylococcus aureus was cultured from her sputum. Mixed pneumonia due to influenza virus, bacteria and fungus was suspected. Although she was treated with medicines for these pathogens, she died from respiratory failure. An autopsy confirmed primary viral pneumonia, Pseudomonas aeruginosa pneumonia and invasive pulmonary aspergillosis. Not only viral pneumonia, but also mixed infections due to bacteria or fungus, might influence the prognosis of 2009 H1N1 influenza infection. These cases indicate the importance of early identification of complicating pathogens and treatment in 2009 H1N1 influenza infection.

We retrospectively analyzed the safety and efficacy of percutaneous cryoablation for the treatment of lung metastasis derived from colorectal cancer. Percutaneous cryoablations were performed on 30 patients over 46 sessions for the treatment of 94 metastatic tumors in the lung field. The local control rate 2 years after cryosurgical treatment was 67%. The 2-years local control rate of a tumor