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On March 28th, 2022, asciminib hydrochloride (Scemblix ® Tablets 20 ‍mg/40 ‍mg), the world's first tyrosine kinase inhibitor (TKI) specifically targeting the ABL myristoyl pocket (STAMP inhibitor), was approved for chronic myeloid leukemia (CML) resistant or intolerant to prior therapy. Asciminib specifically binds to the myristoyl pocket, an allosteric site of BCR::ABL1, and inhibits the ABL1 family molecules. In vitro and in vivo pharmacology studies demonstrated cell growth inhibition and antitumor effects of asciminib. The international phase I study for patients with chronic or accelerated phase CML investigated the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) of asciminib monotherapy. However, the MTD was not reached, so and RDE was determined based on tolerability, safety, pharmacokinetics (PK) and preliminary efficacy data obtained by the time of the study. RDE was determined to be 40 ‍mg twice daily in chronic or accelerated phase CML without T315I mutation, and 200 ‍mg twice daily in chronic or accelerated phase CML with T315I mutation. The international phase III study for patients with chronic phase CML who were previously treated with ≥2 TKIs and resistant or intolerant to the recent treatment demonstrated the superiority of asciminib over bosutinib in achieving the primary endpoint of a major molecular response (MMR) at week 24. Regarding safety, the most common treatment-related adverse event in asciminib arm was thrombocytopenia, and others included neutropenia. Asciminib is expected to be a new treatment option for CML patients who have limited choices due to resistance or intolerance to previous therapies.

This case is a 62-year-old man diagnosed with metastatic renal cell carcinoma. He was referred to our department due to the left renal mass pointed with ultra sound examination. Radiographical examination showed left-side 42 mm renal tumor with multiple lung tumors, suggesting renal cell carcinoma, cT1bN0M1 (pul). As an induction therapy, we selected Pembrolizumab plus Axitinib combination therapy. After 4 course of the therapy, the left kidney tumor shrank to 27 mm, and the lung metastasis disappeared with computed tomography imaging. For the next step, we performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell carcinoma, grade 2 with central necrosis. Since then, complete remission has been maintained without any treatment for 21 months.

Onasemnogene abeparvovec (Zolgensma ® ; formerly AVXS-101) is a one-time gene therapy designed to address the genetic root cause of spinal muscular atrophy (SMA) by replacing the function of the missing or nonworking SMN1 gene via an adeno-associated AAV9 viral vector. On March 19, 2020, the Japanese Ministry of Health, Labor and Welfare approved onasemnogene abeparvovec for the treatment of SMA patients <2 years of age, including presymptomatic patients with a genetic diagnosis. Patients must be negative for elevated anti-AAV9 antibodies. Onasemnogene abeparvovec is administered through a single intravenous infusion, delivering a new working copy of the SMN gene into a patient's cells. Intravenous administration of onasemnogene abeparvovec to SMA model mice resulted in sustained expression of survival motor neuron (SMN) protein, weight gain, improvement of motor function, and prolongation of survival. Its clinical efficacy and safety have been demonstrated through the Phase I START and Phase III STR1VE-US, STR1VE-EU, and SPR1NT trials, and their long-term extension studies. SMA and presymptomatic patients treated with onasemnogene abeparvovec have achieved rates of survival not observed in the natural history of SMA. Treatment has led to rapid motor function improvement, often within one month of dosing, and developmental milestone achievement, including the ability to sit without support. The most commonly observed adverse effects after treatment were elevated liver enzymes, which often resolved with a course of prednisolone, and vomiting. This review discusses the rationale underlying gene replacement therapy for SMA, and describes the basic science, clinical trial experience, and use of onasemnogene abeparvovec.

We report the case of a 74-year-old man with metastatic castration-resistant prostatic cancer (CRPC), who underwent treatment with cabazitaxel. Initially, he underwent docetaxel treatment for 2 years and exhibited severe neuropathy in his hands caused by its toxicity. As a result, we replaced docetaxel with cabazitaxel. On receiving 100% of the dose of cabazitaxel in the first course, febrile neutropenia (FN) was observed on the seventh day. However, he soon recovered from the FN and we began relative dose intensity (RDI) treatment with an adequate dose-volume and interval of treatments. He was successfully administered 51 cabazitaxel treatment courses without severe adverse effects. Cabazitaxel is a highly effective drug used as second-line chemotherapy following docetaxel, and it causes fewer adverse effects compared with docetaxel. Cabazitaxel may be a suitable alternative for outpatient treatment. Given that the patient in this case had a long overall survival of more than 3.5 years and received over 50 courses of cabazitaxel, it is crucial for RDI to be taken very seriously.

Patients who contract severe renal infections often suffer from urosepsis. Therefore, early diagnosis and treatment are required. Sometimes, the treatment with antibiotics is not enough for control of the infections. Most of the patients also require surgical interventions including transurethral drainage and nephrectomy. Twenty-two patients with severe renal infections treated between April 2010 and October 2019 at our institute were evaluated retrospectively. Eleven patients had undergone nephrectomy. Open nephrectomy was performed on 10 patients. Laparoscopic nephrectomy was attempted in the other patient but was converted to open nephrectomy because severe adhesion was found around the tissues. Nephrectomy was performed by the retroperitoneal approach on 9 patients and by the transperitoneal approach on 2 patients. The reteroperitoneal approach was used on two patients who suffered postoperative colon perforation. Inflammatory involvement of renal pelvis, hilum and adjacent structures leads to dense fibrotic reaction and obliteration of tissue planes, which makes the nephrectomy procedure challenging. Therefore, it is important to choose the most appropriate nephrectomy procedure for each patient when they have contracted severe renal infections.

Background/purpose: In a method evaluating conjunctival hyperemia using rabbits, it is common to visually grade the degree of vasodilation. However, this method is limited in evaluating consecutive value and in reproducibility. We quantified the degree of conjunctival hyperemia in rabbits as the area ratio of blood vessels by image analysis, and compared the vascular area percentage calculated by image analysis with the hyperemia score., Methods: The conjunctiva was photographed before and after the instillation of 0.1% arachidonic acid using a digital medical scope VersaCam ® (Nidek Co., Ltd.). Next, the area of the conjunctival blood vessels occupying the area of interest was calculated using hyperemia analysis software. The hyperemia score was visually graded for the degree of conjunctiva vasodilation. Furthermore, the hyperemia score and the vascular area ratio were compared., Results: Fifteen minutes after the instillation of arachidonic acid, the area ratio of the blood vessels in the conjunctiva increased significantly and gradually decreased over time. This trend correlated with the hyperemia score., Conclusion: We found that the degree of conjunctival hyperemia in rabbits can be evaluated numerically and quantitatively. This method is considered to be useful for evaluating conjunctival hyperemia in allergic conjunctival diseases.

The mammalian neocortex contains diverse cell types but whether they organize into repeated modular circuits remains unknown. We discovered that major cell types in neocortical layer 5 form a lattice structure in many areas of the brain. Large-scale three-dimensional imaging revealed that distinct types of excitatory and inhibitory neurons form cell type-specific radial clusters termed microcolumns. Microcolumns form a hexagonal lattice tessellating a wide region of the neocortex. Neurons within individual microcolumns exhibit synchronized in vivo activity and visual responses with similar orientation preference and ocular dominance. During early postnatal development, microcolumns are coupled by cell type-specific gap junctions and later received convergent synaptic inputs. Thus, layer 5 neurons organize into a brain-wide modular system providing a template for cortical processing.

Aim: The Japan Diabetes Society (JDS)/Japan Geriatrics Society (JGS) Joint Committee reported 'Glycemic Targets for Elderly Patients with Diabetes' in 2016. Based on this recommendation, we aimed to clarify 1) the achievement status of glycemic targets in the elderly and 2) the presence of hypoglycemia in real life among elderly individuals with an HbA1c below the lower limit., Subjects and Methods: [Analysis I] In 326 elderly with diabetes ≥65 years of age visiting the outpatient department specializing in diabetes, the proportions of patients with HbA1c values below the lower limit and the use of drugs potentially associated with severe hypoglycemia (e.g. insulin formulations, sulfonylureas, glinides) were investigated. [Analysis II] Of the patients with HbA1c values below the lower limit, seven were tested for hypoglycemia in real life using a continuous glucose monitoring system (CGM)., Results: [Analysis I] Among the 326 subjects, 235 (72.1%) were using drugs potentially associated with severe hypoglycemia, and 63 (19.3%) had an HbA1c value below the lower limit. [Analysis II] In the seven patients examined using CGM, hypoglycemia was detected in five, all of whom were unaware., Conclusions: A considerable number of elderly patients were taking drugs associated with hypoglycemic risks and had an HbA1c value below the lower limit, some of whom actually had hypoglycemia as detected by CGM. Using tools such as CGM, preventive measures against hypoglycemia should be taken.

Tuberous sclerosis complex (TSC) is a genetic disease affecting many organ systems and showing different symptoms in each age group. We encountered a TSC patient with intractable epilepsy who had brain tumors suspected to be subependymal giant cell astrocytoma (SEGA). We used adrenocorticotropic hormone and ordinal antiepileptic drugs at first, but they showed limited effectiveness. After we tried several treatments for epilepsy, we started to use everolimus to prevent tumor growth. As a result, the development of the tumor stopped and the epileptic attack improved simultaneously. The frequency and duration of each epileptic spasm and seizure became milder, and the electroencephalogram findings also improved. The mental development had regressed when the epilepsy started, but it started to progress again after the epileptic attack disappeared. Everolimus may be used for treatment of intractable epilepsy with TSC in patients with a growing SEGA.

We report a case of pancreatic metastasis from prostate cancer. A 65 year-old man developed gross hematuria, and was found to have a markedly elevated PSA and abnormal CT findings indicating mass lesions in bilateral lungs, and pancreatic head, and osteoblastic lesions in pelvic bone. He was referred to the department of Urology and Gastroenterology at Seirei Hamamatsu General Hospital. Digital rectal examination revealed a hen's egg-sized, stony-hard prostate. A systematic needle biopsy of the prostate demonstrated adenocarcinoma (Gleason score 4+4=8). We diagnosed multiple lung and bone metastases from prostate cancer, and suspected that a primary pancreatic ductal carcinoma. The patient was started on an androgen deprivation therapy (ADT) with bicalutamide and degarelix. After 4 months from the initiation of ADT, an MRI of the pancreas showed decreased size of the pancreatic head mass from 18 mm to 7 mm in diameter. We concluded that the pancreatic head mass was metastasis from prostate cancer, and currently continue ADT. Pancreatic metastasis from prostate cancer is very rare, and further accumulation of cases will be required.

(Objectives) To compare efficacy and outcome of urethroplasty for complicated anterior urethral strictures. (Methods) Twelve patients, included 3 boys, with anterior urethral stricture underwent urethroplasty after the failure of either urethral dilatation or internal urethrotomy. We evaluated pre- and post-operative Q max and surgical outcome. (Results) Four patients were treated with end-to-end anastomosis, included a case of bulbar urethral elongation simultaneously, one patient was treated with augmented anastomotic urethroplasty, three patients were treated with onlay urethroplasty with prepucial flap, one patient was treated with tubed urethroplasty with prepucial flap (Ducket procedure) and three patients were treated with onlay urethroplasty with buccal mucosal graft. Postoperative Qmax improved in all patients without major complications and recurrence during follow-up periods ranging from 17 to 102 months (mean 55 months). (Conclusions) Urethroplasty is an effective therapeutic procedure for complicated anterior urethral stricture.

A 68-year-old man underwent radical nephrectomy for renal cell carcinoma of the right kidney 12 years ago. He was diagnosed as having a recurrent tumor of the contralateral kidney and a single metastatic pulmonary lesion by diagnostic imaging on the annual checkup. He visited us in order to receive nephron sparing surgery. Since the preoperative abdominal computed tomography showed tumor thrombus invading into the intrarenal vein, ex vivo partial nephrectomy and auto-transplantation was performed. Although he received transit hemodialysis during the postoperative 10 days, his renal function, thereafter became stable without hemodialysis. Eighty-seven days later he underwent right lower lobectomy. At postoperative 6 months he has no local recurrence or distant metastasis and maintains well-preserved renal function.

A 61-year-old man was diagnosed with lung squamous cell carcinoma in the lower lobe of the right lung. He had received first-line chemotherapy consisting of cisplatin and docetaxel (DTX); however, an allergic/hypersensitivity reaction occurred shortly after administration of the second course of DTX. Thirty-nine months later, he received nanoparticle albumin-bound paclitaxel (nab-PTX) as sixth-line chemotherapy, which did not produce a hypersensitivity reaction. Hypersensitivity after DTX administration may have been due to the DTX vehicle. Therefore, nab-PTX administered under close supervision is a valid therapeutic option in similar cases.

Bone is one of the most preferential metastatic target sites for cancers. The biological crosstalk between metastatic cancer cells and bone microenvironment is critical to the pathophysiology of bone metastases. For example, It is well established that PTH-rP production in cancer cells stimulated by bone-derived TGF-β facilitates bone metastasis through promoting bone resorption by osteoclasts, thereby establishing "vicious cycle" between metastatic cancer cells and bone. In addition, recent studies identified several new players including platelets and MDSCs which contribute to the development of bone metastasis. In this review, we will overview the current topics on the mechanism by which bone metastasis is modulated at cellular and molecular levels.

It has been passed 10 years since the first article of bisphosphonate-related osteonecrosis of the jaw (BRONJ) was reported in 2003. During this period of time, turmoil and confusion initially seen in physicians, dentists and patients in the management of BRONJ have been gradually and significantly settling and preventive methods for BRONJ have been developed to some extent due to the accumulation of substantial amounts of information and clinical experience. Further, Japanese version of position paper for BRONJ that suggests unified view of the pathophysiology of BRONJ and consistent treatments of BRONJ was published in 2010 and 2012. However, the mechanism and pathophysiology of BRONJ still remain elusive. The recognition for BRONJ is still inconsistent between physicians and dentists. It is also noted that a new anti-resorptive drug denosumab is associated with ONJ. Thus, there are still lots to learn and study. In this chapter current our understanding of BRONJ will be described.

Solid cancers such as breast, prostate and lung cancer have a predilection for spreading to bone. Accumulating data suggest that the crosstalk between metastatic cancer cells and bone-resorbing osteoclasts plays a central role in the development and progression of bone metastases. Recent studies have revealed that osteoblasts mediate this crosstalk by expressing the receptor activator of NF-kappaB ligand (RANKL) in response to cancer-produced osteotropic factors. The RANKL promotes osteoclast formation and bone resorption via the binding to RANK expressed in hematopoietic osteoclast precursor cells and mature osteoclasts. Denosumab is the humanized anti-RANKL neutralizing monoclonal antibody and thus would be a specific and effective therapeutic agent for the treatment of bone metastases. In fact, clinical studies clearly demonstrated that denosumab significantly inhibited the development of skeletal-related events associated with bone metastases and indicate its usefulness for bone metastases.

Various three-dimensional fast spin echo (3D-FSE) sequences are used for non-contrast magnetic resonance angiography (MRA). Differences in the ability to detect vascular stenosis using these sequences, however, have not yet been evaluated. The purpose of this study is to evaluate the usefulness of each sequence for the detection of vascular stenosis by using a vascular phantom. The phantom consisting of silicon tubes with 30% and 70% stenosis of luminal diameter and fluids close to T2 value of blood were used for the study. Non-contrast MRA with half-Fourier acquisition single-shot turbo spin echo (HASTE)-noncontrast magnetic resonance angiography of arteries and veins (NATIVE), sampling perfection with application optimized contrasts using different flip angle evolutions (SPACE)-NATIVE, fresh blood imaging (FBI) and triggered angiography non contrast enhanced (TRANCE) sequences was performed by using the phantom which can be varied in terms of the steady flow velocity. Each stenosis was quantitatively estimated by the stenosis index (SI) calculated from the signal intensities on acquired images. The signal intensity of the non-stenotic vascular site markedly decreased at more than a flow rate of 20 cm/s in all sequences. Significant decrease in the signal intensity was observed in the distal point from the stenosis area on these images acquired by using HASTE-NATIVE and FBI sequences. FBI and TRANCE sequences showed a more accurate SI for 30% stenosis than HASTE-NATIVE and SPACE-NATIVE sequences. SI for 70% stenosis was overestimated in all sequences at 5 cm/s of diastolic flow rate. In conclusion, the ability to detect vascular stenosis on non-contrast MRA image using 3D-FSE sequences depends on the image quality during diastolic phase in the cardiac cycle. FBI and TRANCE sequences are useful to detect the mild arterial stenosis.

Bone formation is the key for successful dental treatments including periodontal tissue regeneration osseointegration of implant placement in which new alveolar bone formation is mandatory. Parathyroid hormone (PTH) is a peptide hormone containing 84 amino acids. Accumulated results show that intermittent PTH administration increases bone mass. Accordingly, recombinant N-terminal fragment of human PTH (1-34) , Teriparatide, is used for the treatments of osteoporosis worldwide. It is, therefore, expected that PTH has the potential to be a new therapeutic intervention for oral diseases that require increased bone remodeling and new bone formation.

Bone metastasis is relatively common in patients with breast, prostate, and lung cancer, and may cause severe bone pain, pathological fractures, hypercalcemia and other bone-related complications that drastically undermine quality of life. The currently-available treatments for bone metastasis are unsatisfactory in their effectiveness and outcome. Bone continuously undergoes remodeling through a repeated cycle of osteoclastic bone resorption and osteoblastic bone formation. When cancer cells metastasize to the bone, their growth is promoted under the influence of a variety of growth factors that are supplied from the bone as a consequence of osteoclastic bone resorption. This, in turn, causes an increased production of osteoclast- and osteoblast-stimulating cytokines in these cancer cells, leading to a further increase in bone remodeling. This vicious cycle between bone and metastatic cancer cells supports the development and progression of bone metastases. Accumulating evidence shows that RANKL, a cytokine expressed in osteoblasts/bone marrow stromal cells, plays an important role in the formation, activation, and survival of osteoclasts, which are key players in bone remodeling. RANKL is thus expected to inhibit bone metastasis by disrupting this vicious cycle, and is considered a rational new therapeutic intervention for bone metastasis. In animal models, inhibition with RANKL has been shown to prevent the development of bone metastases. Based on the promising results from these preclinical studies, a fully human monoclonal anti-RANKL antibody, denosumab, has been developed. In three phase III clinical trials of denosumab versus zoledronic acid(ZA)in advanced cancer patients with bone metastases, denosumab was superior or equal to ZA in delaying the time to the first on-study skeletal-related events(SRE). In conclusion, denosumab, a fully human monoclonal anti-RANKL antibody with a targeted mechanism of action, enables us to more easily and effectively treat bone metastases and manage cancer patients with bone metastases.

Breast cancer has a predilection for spreading to bone. Accumulating data suggest that the interactions between breast cancer cells and bone-resorbing osteoclasts mediated initially by bone-derived growth factors and consequently by RANKL in osteoblasts and RANK in pre-osteoclasts are critical to the development and progression of bone metastases. In addition, recent studies have revealed that breast cancer cells strongly express RANK and thereby can be directly influenced by osteoblast-derived RANKL. These results warrant the use of the humanized anti-RANKL neutralizing antibody (denosumab) as a specific and more effective therapeutic agent for the treatment of bone metastasis in breast cancer patients.

Bone, as well as the lung and liver, is among the sites of predilection for cancer metastasis. The bone stores large amounts of growth factors such as insulin-like growth factors and transforming growth factor-b, and provides fertile soil for metastatic cancer cells by continuously releasing these bone-stored growth factors, which are a consequence of osteoclastic bone resorption. Metastatic cancer cells in turn produce osteoclast-stimulating cytokines such as parathyroid hormone-related protein( PTH-rP), prostaglandin E2.(PGE2), and various interleukins(ILs). These cancer-produced osteoclast-stimulating cytokines bind to their cognitive receptors and promote the expression of ligands for the receptor activators of nuclear factor kB (RANKL)in osteoblasts. RANKL then binds to its receptor RANK, expressed in pre-osteoclasts, stimulates mature osteoclast formation, and subsequently, osteoclastic bone resorption. This vicious cycle between metastatic cancer cells and osteoclasts is critical to the development and progression of bone metastases. In addition, it is likely that metastatic cancer cells are influenced by bone environments(or niche)and acquire additional capacities such as an epithelial-mesenchymal transition(EMT), allowing them to be resistant to chemotherapy or apoptosis, to survive in a dormant state, or to aggressively spread to distant organs including lung and liver. Thus, the bone can serve as transit port. Disrupting this cycle by inhibiting osteoclastic bone resorption, antagonizing bone-derived growth factors, and neutralizing RANKL or PTH-rP, should be a promising therapeutic intervention for bone metastases. Bisphosphonates(BP)are specific inhibitors of osteoclasts, and have been shown to significantly reduce skeletal-related events(SRE)associated with bone metastasis. Denosumab is a neutralizing monoclonal antibody to RANKL and has recently been found to inhibit SRE more effectively than BP. Further understanding of the crosstalk communication between metastatic cancer cells and bone at the molecular level should lead us to design novel, more effective and specific treatments for cancer patients with bone metastases.

Bone pain is the most common complications in bone metastases, causing increased morbidity and undermining quality of life (QOL) in patients. It has been considered that algesic factors produced by tumor tissues and nerve injury are involved in pain progression. However, the molecular mechanisms of bone pain are still complex and not fully understood. Recent studies show that acidic microenvironment created in bone metastasis is relevant to pain signal through the activation of acid-sensing nociceptor in sensory neurons. These elucidations might be lead to the development of therapeutic approaches for cancer pain.

Bone is one of the most preferential metastatic target sites for cancers. However, based on the anatomical structure of the vascular system, bone is not recognized as a preferential metastatic target. Therefore, the biological crosstalk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. Bone microenvironments possess unique biological features characterized by abundant growth factors and diverse cellular network including osteoblasts, osteoclasts and hematopietic cells. Cancers develop bone metastases by utilizing these unique bone environments for colonization and bone destruction. Better understandings of precise molecular mechanisms underlying cancer and bone crosstalk would contribute to the development of new therapeutic approaches for the treatment of bone metastasis at molecular levels.

A 50-year-old woman visited our department for further examination of incidental bladder tumor detected by ultrasound at her health check. Cystoscopy demonstrated a submucosal tumor in the anterior wall of the urinary bladder. Magnetic resonance imaging revealed that the tumor had high intensity in T2- weighted images. The slightly-elevated serum level of dopamine and uptake image in the meta iodobenzyl granidine-scintigraphy test suggested that she might have ectopic pheochromocytoma in the urinary bladder. Partial cystectomy with extirpation of the tumor was performed. The histological diagnosis was schwannoma, which is rarely found in the urinary bladder.

Patients with cancers such as breast or prostate cancer who have been treated with hormone deprivation therapies or anti-cancer agents for certain periods of time frequently manifest reduced bone mass or pathological fractures during their clinical course. These are likely due to an imbalance between osteoblastic bone formation and osteoclastic bone resorption resulting from hypogonadism. Bone should be carefully monitored in cancer patients who are going to continually receive adjuvant hormonal or anti-cancer therapies. Administration of anti-bone resorption agents such as bisphosphonates may be necessary to maintain bone mineral density and protect pathological fractures in these cancer patients.

By input of the actual dose of a drug given into a radiology information system, the system converting with an accounting system into a cost of the drug from the actual dose in the electronic medical record was built. In the drug master, the first unit was set as the cost of the drug, and we set the second unit as the actual dose. The second unit in the radiology information system was received by the accounting system through electronic medical record. In the accounting system, the actual dose was changed into the cost of the drug using the dose of conversion to the first unit. The actual dose was recorded on a radiology information system and electronic medical record. The actual dose was indicated on the accounting system, and the cost for the drug was calculated. About the actual dose of drug, cooperation of the information in a radiology information system and electronic medical record were completed. It was possible to decide the volume of drug from the correct dose of drug at the previous inspection. If it is necessary for the patient to have another treatment of medicine, it is important to know the actual dose of drug given. Moreover, authenticity of electronic medical record based on a statute has also improved.

A 63-year-old man with a history of therapy for asthma was admitted to a neighborhood hospital for treatment of a lower limb blister, accompanied by edema, pain and systemic fever. Churg-Strauss syndrome was diagnosed based on an increase in peripheral blood eosinophils, positive MPO-ANCA and other findings. He was given an injection of methylprednisolone sodium succinate; however his lower limb pain, fever and peripheral blood eosinophilia worsened. Therefore, steroid-resistant Churg-Strauss syndrome was diagnosed, for which he was referred to our hospital for more intensive treatment. His lower limb pain, fever, peripheral blood eosinophilia and inflammatory reactions improved immediately after switching treatment to oral prednisolone. Since a challenge test using an intravenous infusion of methylprednisolone sodium succinate worsened the lower limb pain, fever and peripheral blood eosinophilia, a drug allergy was diagnosed together with Churg-Strauss syndrome.

The incidence of endometrial cancer and ovarian cancer has increased in Japan, during the last decade. On the other hand, the incidence of cervical cancer has declined until the middle of the 1990's. However, in recent years it has been increasing slightly. Change of Japanese women's lifestyle may contribute to the increase in gynecologic cancer incidence in Japan. Infection with high-risk oncogenic human papilloma viruses (HPV) play an important role in cervical carcinogenesis. Advances in understanding of the role of HPV in the etiology of cervical cancer have led to the development, evaluation and recommendation of HPV vaccines. Recently environmental factor and genetic factor related carcinogenesis and development have been investigated of gynecologic cancer. This review provides a summary of these studies about the etiology, the treatment and prevention against gynecologic cancer.

A 67-year-old man was scheduled for resection of thoracic intramedullary tumor. His blood type was AB. Unexpectedly rapid and massive hemorrhage occurred during the operation. We infused a large amount of crystalloid, colloid, and 5% albumin. But he went into circulatory collapse before we could get type AB red blood cell (RBC) and hemoglobin was reduced to 3.8 g x dl(-1). We decided to transfuse 4 units of ABO incompatible type O RBC. Later, type AB RBC and other blood components became available and the patient recovered. We conclude that transfusion of ABO incompatible blood in patient with critical hemorrhage should be encouraged to save life.

Purpose: Staging for prostate cancer often includes computed tomography (CT) and bone scan in Japan. We examined the criteria of avoiding unnecessary CT and bone scan for the prostate cancer patients at Matsusaka Chuo General Hospital., Subjects and Methods: 211 patients were newly diagnosed at our institution between 1998 September and 2004 April. We reviewed data from 208 patients who had a staging CT and bone scan. The data was analysed using Gleason score, clinical T-stage and serum prostatic specific antigen (PSA) level., Results: CT detected lymphadenopathy in 19 patients (9.1%), Bone scan detected bone metastasis in 31 patients (14.9%). However there was no lymphadenopathy detected by CT in the patients with 20 ng/ml or less. In the analysis using PSA and Gleason score, there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and Gleason sum 7 or less. In the analysis using PSA and clinical local stage there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and localized lesion (cT1-2)., Conclusion: In a new proatate cancer patient CT and bone scan can be avoidable by PSA level of 20 ng/ml or less and cT1-2 or less and Gleason sum 7 or less.

Clinically, fatty marrow, accumulation of adipocytes in bone marrow, is often observed in the patients who manifest bone diseases such as osteoporosis. Since adipocytes and osteoblasts are differentiated from mesenchymal stem cells, it would be clinically and biologically important to understand regulatory mechanisms of the balance between adipogenesis and osteoblastogenesis. Recently, experimental findings indicated the involvement of adipokines including leptin and adiponectin in bone metabolisms. Thus, adipocytes appear to play a role in regulation of bone metabolisms.

Phosphate is a second most abundant mineral next to calcium. The facts that hypophosphatemia is associated with the retardation of skeletal development and phosphate levels increase during endochondral ossification suggest that phosphate plays a role in cartilage differentiation. The type 3 sodium-dependent phosphate transporter (NPT3) expressed in growth plate chondrocytes transports extracellular phosphates into the cells. These phosphates are utilized for ATP synthesis, which in turn promotes apoptosis of growth plate chondrocytes through activation of the caspase signal pathways. Subsequently, matrix vesicles released from apoptotic chondrocytes accelerate calcification of chondrocytes. Our results suggest that phosphate plays a critical role in terminal differentiation of chondrocytes.

Recently, large body of evidences that Wnt plays an important role in regulation of tissue patterning and skeletogenesis including membranous and enchondral ossification is accumulating. Several genetic studies also indicate that low density lipoprotein receptor related protein (LRP) 5, LRP6, beta-catenin and lymphoid enhancer-binding factor/T-cell factor (LEF/TCF) participate in osteogenic action induced by Wnt family members. In contrast, secreted Frizzled-related proteins and dickkopf (Dkk) proteins, natural Wnt inhibitory factors, inhibit Wnt-dependent osteogenesis, presumably functioning as a negative feedback loop. In addition, Wnt signaling interacts with BMP signaling, thereby modulating its osteogenic action. Thus, the network systems of Wnt signaling temporally and spatially controls osteogenic action of Wnt family members.

Bone pain is one of the major complications of bone metastases and profoundly deteriorates quality of life in cancer patients. It has been suggested that the nerve injuries by tumor invasion and the inflammatory factors secreted by cancer cells are involved in the pathophysiology of bone pain. Recent studies including ours suggest that the activation of acid-sensing receptors by tumor-induced acidosis in bone metastases also plays a part in causing bone pain. In this review, the current understanding of the mechanisms of cancer-induced bone pain is discussed.

Bone is one of the most preferential metastatic target sites for solid cancers such as breast, prostate and lung cancers. Although the precise molecular mechanisms underlying this predilection are still unclear, it appears that these cancer cells possess the capacity to modulate bone microenvironments to facilitate their arrest, survival and proliferation. In particular, production of bone-resorbing cytokines by these metastatic cancer cells increases osteoclastic bone resorption, which in turn promotes the colonization of these cancer cells in bone through releasing bone-stored growth factors into the bone marrow cavity. This crosstalk between metastatic cancer cells and bone stimulates the development and progression of bone metastases. Disruption of this vicious cycle leads us to design effective and specific interventions for osteolytic bone metastases of solid cancers.

We report a long-term survival case of Arima syndrome requiring hemodialysis. The patient, now 25 years of age, was hypotonic at birth. She was diagnosed with Dandy-Walker syndrome at an early month of age when she underwent posterior cranial fossa cystectomy and vermian agenesis was confirmed. With some delay in psychomotor development, she showed the development of language comprehension and meaningful speech and started to walk without aid at the age of 7 years. Polycystic kidneys were found at 11 years, and Arima syndrome was diagnosed at 16 years when she presented herself to our hospital with rupture of esophageal varices. With progressive deterioration of renal function, she was placed on chronic hemodialysis at 23 years. She presented short stature, right blepharoptosis and telecanthus on physical examination; pancytopenia, liver dysfunction and renal failure on laboratory studies agenesis of cerebellar vermis on magnetic resonance imaging reduced amplitude of electroretinographic response, and retinal pigmentary changes under funduscopy. Hemodialysis was initiated uneventfully except that nafamostat mesilate was used as anticoagulant because of her bleeding tendency. Arima syndrome, also known as cerebro-oculo-hepato-renal syndrome, is a disorder characterized by cerebellar vermis aplasia and other clinical features such as profound psychomotor retardation, severe visual impairment, characteristic facial appearance with blepharoptosis, hepatic fibrosis and progressive renal insufficiency. The clinical findings of our patient were consistent with Arima syndrome though her psychomotor retardation and visual impairment were relatively moderate as compared with those previously reported. As most patients with Arima syndrome may die of uremia in their early teens, dialysis therapy should be considered to improve the patient's survival and quality of life depending on the severity of psychomotor retardation and other systemic disorders.

Bone is one of the most preferential metastatic target sites for cancers such as breast, prostate and lung cancers. Although the precise molecular mechanisms underlying this predilection are still unclear, it appears that these cancer cells possess the capacity to modulate bone microenvironments for them to arrest, survive and proliferate. In particular, the production of bone-resorbing cytokines by these cancer cells increases osteoclastic bone resorption, which in turn facilitates the colonization of these cancer cells in bone through abundant supplies of bone-stored growth factors. This crosstalk between metastatic cancer cells and bone promotes the development and progression of bone metastases. Disruption of this vicious cycle using bisphosphonates will allow us to effectively and specifically inhibit bone metastases.

In recent years, by making digitally reconstructed radiographs (DRR) from helical CT images in the position check of an irradiation field, the verification performed by DRR, lineacgraphy (LG), or an electronic portal imaging device (EPID) has become possible. We examined the optimal parameters of single-slice helical scanning in DRR image construction and the usefulness of DRR replaced with the simulation film. We performed a section sensitivity profile at the Z-axis (SSPz) as evaluation of a physical characteristic of helical CT equipment and the form of image of DRR, fixed quantity evaluation of imaging distortion, and visual verification of images. It was determined that DRR was influenced by the partial volume effect depending on slice thickness and pitch, such that this influence occurred when slice thickness and pitch were large. Between a simulation film and DRR reconstructed using imaging parameters with a slice thickness of 3 mm, pitch of 1.0, and reconstruction slice thickness of 3 mm, coincidence was not complete. However, the distortion of DRR was small and the difference was not statistically; thus it was considered to be useful. In conclusion, we consider that DRR reconstructed using the parameters of single-slice helical scanning is useful for clinical evaluation in radiotherapy planning.

The patient was a 21-year-old woman who, at 16 years old, had had no subjective symptoms. She was referred to our hospital because of abnormal shadows in the middle of the left lung that were seen on a chest radiograph during a school medical screening. In her first examination at our hospital, CT revealed tumor-like shadows with diameters of 2.0 cm in Lt-S6 and 0.5 cm in Rt-S5, together with arteries and veins. Lung ventilation and blood flow scintigraphy was used to obtain images of both kidneys and the head, and as a result, a pulmonary arteriovenous malformation (PAVM) was diagnosed. Because of a low shunt fraction of 10.8%, the patient was only kept under observation. However, at 21 years of age, she complained of dyspnea with exercise and was admitted to the hospital for further examination. Chest CT showed an increase in the diameter of the arteriovenous malformation (AVM) to 2.7 cm, and 3-D image reconstruction clearly revealed the position of the tumor in relation to the pulmonary artery and vein. The shunt fraction had increased to 18.3%. Coil embolization was therefore performed to A6b, the artery feeding the AVM (using interlocking detachable coils of 6 mm-10 cm and 8 mm-20 cm, and Trufill coils of two 7 mm-6 cm and 5 mm-4 cm). The patient had no serious postoperative complications. A decreased AVM diameter of 1.7 cm and an improved shunt fraction of 11% were observed, and she was discharged from the hospital. Since then, she has been well, without dyspnea, and her chest films show only coils and no aggravation of other AVMs. AVMs generally have no symptoms, but they can cause severe complications such as hypoxia from a right-to-left shunt, hemoptysis, hemothorax, and brain abscesses. Coil embolization should be considered more often for the treatment of AVM because it is safer, more effective and less invasive than traditional operations.

Malignant cells non-randomly and preferentially disseminate to certain distant organs. Of note, breast, prostate and lung cancer and multiple myeloma have a strong predilection for spreading to bone. One of the proposed mechanisms is that these cancer cells express receptors and corresponding cell adhesion molecules (CAMs) for the extracellular matrices (ECMs) and CAMs that are present in the bone microenvironment. Here, the role of integrins and cadherins in bone metastasis will be described.

We report a case of pleural malignant lymphoma associated with chronic tuberculous pyothorax. A 67-year-old male was hospitalized because of left lateral chest swelling and pain. He had suffered from pulmonary tuberculosis at the age of six and tuberculous pleurisy at the age of 24. We made a histologic diagnosis of malignant lymphoma diffuse large B-cell type. He was medicated THP-COP (THP, CY, VCR, PSL) therapy and his chest pain and swelling has improved gradually. From the view point of molecular biology, we detected Epstein-Barr virus (EBV) infection in the pyothorax wall. In conclusion, we should be more careful about medical examination in patients with EBV positive tuberculous pyothorax considering the complication of malignant lymphoma.

A study was made on the relation between active pulmonary tuberculosis and underlying diseases in 119 tuberculosis patients. Out of total 119 patients, 87 patients (73.1%) had underlying diseases. The most common underlying disease was diabetes mellitus in 34 patients (39.1%), followed by HCV (+) chronic hepatitis, sequela of cerebral infarction, hypertension and gastric ulcer. In patients who had underlying diseases, the mean age was higher, proportion of sputum smear positive cases was higher, albumin was lower, and period until sputum culture negative conversion was longer. In patients who had diabetes mellitus, proportion of cases with cavity on chest X-P was higher, and in patients who had sequela of cerebral infarction or hypertension, mean age was higher. In patients who had diabetes mellitus and whose HbA1C was > or = 9%, proportion of smear positive cases was higher, albumin was lower and period until culture negative conversion was longer than in patients who had diabetes mellitus and whose HbA1c was < 9%, suggesting that control of blood sugar in diabetes mellitus related to severity of pulmonary tuberculosis. In patients who had diabetes mellitus and whose albumin was < 3 g/dl, period until culture negative conversion was longer than in patients who had diabetes mellitus and whose albumin was > or = 3 g/dl. In patients who had underlying diseases, these diseases caused decline of tuberculous immunity and nutritional disturbance represented by lower albumin also promoted decline of tuberculous immunity. It is suggested that the underlying diseases affected the onset and progression of pulmonary tuberculosis.

A 67-year-old man, who had undergone left nephroureterectomy for ureteral tumor (transitional cell carcinoma, G1) eight years previously, was found to have two renal tumors in the residual right kidney by the follow-up computed tomography (CT). We performed non-ischemic enucleation for multiple tumors at the upper and lower pole in the unilateral kidney using a microwave tissue coagulator (MTC). We confirmed by means of ultrasonography during operation the absence of any other satellite tumors. The operation time was 154 minutes and bleeding during operation was 267 ml. There was no difference between creatinine before (0.73 mg/dl) and after (0.79 mg/dl) operation. On the follow-up CT, there was a low density area after enucleation. This area gradually decreased and disappeared on enhanced CT 18 months after operation. We enucleated multiple renal cell carcinomas using MTC without reduction of renal function or remarkable side effects. These results suggested that non-ischemic enucleation using MTC would be useful for multiple renal cell carcinoma in the unilateral kidney.