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A 77-year-old man visited a clinic because of nausea and chest discomfort. On blood test, hepatobiliary enzymes were elevated, and he referred to our hospital. Contrast-enhanced CT revealed stenosis of the extrahepatic bile duct and brush cytology of the bile duct showed adenocarcinoma. We therefore performed pancreatoduodenectomy for extrahepatic bile duct cancer. Pathological diagnosis was small cell neuroendocrine carcinoma, pT3N2M0, Stage ⅢA. The patient did not receive adjuvant chemotherapy and 3 months later contrast-enhanced CT and MRI showed multiple liver metastases. The patient was treated with cisplatin plus irinotecan in the first-line, cisplatin plus etoposide in the second-line, and amrubicin in the third-line and accordingly he died 1 year and 3 months after the surgery. Chemotherapy for neuroendocrine carcinoma of the bile duct is recommended as in small cell lung cancer, but the prognosis is extremely poor. We report this case with a review of some of the literature.

CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promise as treatment of relapsed or refractory B-cell malignancies. However, the clinical utility of early CAR-T monitoring within 1 month after infusion has not been elucidated. In this study, we quantitatively measured CAR-T kinetics in peripheral blood on days 2, 4, 7, 9, 11, 14, 21, and 28 post-infusion using flow cytometry and quantitative polymerase chain reaction in 13 patients with relapsed refractory diffuse large B-cell lymphoma (DLBCL) treated with tisagenlecleucel (tisa-cel). No relationships were identified between bulk CAR-T kinetics and treatment outcomes. Interestingly, the magnitude of CD4 + CAR-T expansion was higher in responders than in nonresponders, while CD8 + CAR-T expansion was minimal in responders. Additionally, CAR-T proliferation was more pronounced in patients with cytokine release syndrome. Our results suggest that CD4 + CAR-T cellular kinetics within 1 month after CAR-T infusion may predict its efficacy after tisa-cel therapy in adult patients with DLBCL.

(Objective) Pregnancy in kidney transplant recipient continues to remain challenging due to a high rate of cesarean section along with preterm delivery, and concern for worsening renal function. This study examined the prognosis and perinatal management of post-transplant pregnancies. (Patients and methods) A total of nine post-transplant recipients at Niigata University Medical and Dental Hospital between 2007 and 2021 were retrospectively examined. (Results) All pregnancies were planned. Calcineurin inhibitors and steroids were continued, and antimetabolites were changed to azathioprine. The mean age at delivery was 33±3.8 years, and the mean time from renal transplantation to delivery was 6.5±3.5 years. Five patients (55.5%) had cesarean sections, while four (44.5%) patients had normal vaginal deliveries. The mean gestational age was 35±3.0 weeks, and the mean birth weight was 2,336±565.4 g. No congenital malformation was observed. The most common reason for early delivery was worsening renal function, seen in six (66.7%) patients. The mean serum creatinine level before pregnancy was 1.11±0.23 mg/dL and then worsened to 1.59±0.37 mg/dL during pregnancy. However, it recovered to 1.14±0.40 mg/dL after delivery. One patient had antibody-mediated rejection with donor specific antibody (DSA) prior to pregnancy, and her renal graft function worsened slightly after delivery. Another patient had a de novo DSA after delivery, which was not detected before pregnancy. (Conclusions) In our hospital, pregnancy in kidney transplant recipients were safe and renal graft function after delivery was relatively stable. Patients may require adjustment of calcineurin inhibitors during pregnancy, and the appearance of DSA after delivery should be noted.

According to the risk classification of recurrence, the standard treatment for gastrointestinal stromal tumor(GIST)is complete surgical resection and postoperative adjuvant therapy with imatinib; however, the usefulness of neoadjuvant therapy is unclear. We report a case of giant GIST in the pelvis suspectedly having bladder infiltration that was radically resected and underwent preoperative imatinib therapy. A 52-year-old man visited a clinic because of abdominal pain, fever, and frequent urination. An abdominal mass was determined, and the patient was referred to our hospital for detailed examination and treatment. Contrast-enhanced CT revealed a 17 cm diameter irregular mass from the lower navel to the pelvis, and the bladder boundary was partially unclear. Transrectal biopsy was performed using endoscopic ultrasonography, and according to the Fletcher classification, a high-risk GIST was diagnosed. After preoperative imatinib therapy of 400 mg/day was administered for 3 months, surgery was performed. The tumor was strongly adhered to the bladder, but no invasion was observed, and partial small intestine resection was performed. The surgical margin was negative without capsule damage. On day 34 postoperatively, imatinib therapy was resumed, and as of 1 year postoperatively, the course is well without recurrence.

Levodopa-carbidopa intestinal gel (LCIG) therapy has been established as a device-aided treatment for advanced Parkinson's disease. We retrospectively investigated the issues related to LCIG therapy in patients with Parkinson's disease at our hospital from March 2014 to July 2018. The subjects were 18 patients including nine men and nine women. The mean duration of PD symptoms and motor fluctuation was 14.5 ± 5.9 and 7.2 ± 4.5 years, respectively. The mean age at initiation of LCIG was 60.1 ± 9.4 years and the mean treatment period was 21.1 ± 19.5 months. One hundred and sixteen LCIG-associated issues were observed, including pain at the gastrostomy site (23 cases), hypergranulation tissue (14 cases), skin redness and/or erosions (11 cases), cutaneous infections at the gastrostomy site (eight cases), percutaneous endoscopic gastrojejunostomy (PEG-J) tube occlusion in the gastrointestinal tract (19 cases), irremovable PEG-J tube (13 cases), dislocation of the PEG-J tube (six cases), and breakage of the connector (eight cases). The majority of these issues were easily diagnosed and could be managed by neurologists who are familiar with LCIG therapy.

A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

Dust indicators based on light scattering photometers are widely used to measure aerosol concentrations in work environments. These concentrations at workplaces in Japan are measured by these dust indicators and calibrated by mass concentration in order to control workers' exposure to dust. The mass concentration in a specific point in a workplace is measured simultaneously with a dust indicator. The mass concentration of the respirable fraction of dust particles should be determined by the gravimetric method with low volume air samplers or other devices, but some dust indicators are not equipped with a size separator for respirable fraction, and we used to get unstable results at the calibration. In this study, we designed miniature cyclones for a dust indicator and evaluated their performances of respirable fraction and PM 2.5 fraction.

We conducted a questionnaire survey to collect epidemiological information on patients with Scans Without Evidence of Dopaminergic Deficit (SWEDD). We sent questionnaires to 4,970 neurology specialists in Japan in July 2015 and received responses from 933 of them. The total number of patients reported to have Parkinson's disease was 39,532, which included 237 cases of SWEDD in patients (111 males, 125 females, and 1 case without a gender description). The disease duration in patients with SWEDD was short; 127 cases (53.6%) had a duration less than 3 years, and 78 cases (32.9%) had a duration of 3 years or more but less than 7 years. By age, 59 cases (24.9%) occurred in individuals in their 60s, and 106 cases (44.7%) occurred in individuals in their 70s. Sixty-three neurologists stated that they performed dopamine transporter single photon emission computed tomography (DaT SPECT) on almost all patients with Parkinson's disease. They treated a total of 3,600 patients with Parkinson's disease which included 107 cases of SWEDD; therefore, approximately 3.0% of Parkinson's patients were estimated have SWEDD. The causes of SWEDD were unknown (101 cases), essential tremor (22 cases), vascular Parkinsonism (14 cases), and drug-induced Parkinsonism (14 cases). The majority of neurologists had doubts about the diagnosis of Parkinson's disease prior to confirming the diagnosis using DaT SPECT for reasons such as: normal findings on meta-iodobenzylguanidine (MIBG) myocardial scintigraphy, poor responses to anti-Parkinson drugs, lack of true akinesia, unchanged symptoms, and atypical symptoms. Two hundred and nineteen cases included reports on treatment paradigms following the SWEDD diagnosis. Of those cases, patients in 159 cases were maintained on the same treatment following diagnosis.

We report a rare case of ruptured coronary artery aneurysm. A 58-year-old woman experienced a sudden chest pain. Coronary arteriography( CAG) and computed tomography(CT) showed pericardial effusion and 2 saccular coronary artery aneurysms connected by a communicating artery. The 1st one was originated from the right coronary artery and flowed to the communicating artery. The 2nd one was originated from both the diagonal branch and the communicating artery, and flowed to the main pulmonary artery, forming a fistula. Since the 1st one was larger, it was suspected to be the rupture site. Emergency operation was performed and the aneurysms were directly closed under cardiopulmonary bypass. The postoperative course was uneventful.

Acute graft-versus-host disease (GVHD) is diagnosed by the presence of, at least, one of the skin, liver, and gut damage and the absence of a disease similar to it. Except upper gastrointestinal GVHD, acute GVHD is diagnosed on the basis of clinical findings. The diagnosis via biopsy does not necessarily coincide with the clinical diagnosis of acute GVHD. Although the systemic grade is categorized according to the organ stage, it does not accurately reflect the treatment response or prognosis. The identification of GVHD biomarker is currently being intensively investigated to supplement the insufficient risk stratification. Perhaps, the establishment of risk stratification that can accurately reflect the treatment response and prognosis may change the acute GVHD therapy into stratified therapy.

A 26-year-old man presented with fever, multiple lymphadenopathies, polyclonal hypergammaglobulinemia, and an elevated serum interleukin-6 (IL-6) level. Multicentric Castleman disease (MCD) was diagnosed by lymph node biopsy. Treatment with prednisolone (PSL) was initiated; however, its efficacy was limited. During PSL tapering, rapidly progressive anemia and thrombocytopenia developed concurrently with increased reticulocyte level, elevated serum LDH level, decreased haptoglobin level, and positive direct Coombs test. Based on these findings, Evans syndrome, which is a concurrent development of autoimmune hemolytic anemia and immune thrombocytopenia, was confirmed. The PSL dose was increased but was ineffective. Therefore, treatment with tocilizumab was initiated, and the clinical findings of both MCD and Evans syndrome improved. The clinical course of this case suggests that tocilizumab could be a treatment option for Evans syndrome complicated with MCD. Three other cases of Evans syndrome complicated with MCD have also been reported; however, this is the first case that shows the efficacy of tocilizumab as treatment for both MCD and Evans syndrome.

An 18-year-old man was diagnosed with Epstein-Barr virus (EBV) -associated hemophagocytic syndrome (HPS) and treated with prednisolone (PSL) at a previous hospital. During PSL tapering, the HPS symptoms reappeared, and the patient was referred to our hospital. Increased PSL improved the symptoms, but the EBV infection remained unresolved. At age 20, he was admitted to our hospital for newly developed pneumonia and diagnosed with myelodysplastic syndrome (refractory cytopenia with multilineage dysplasia) (MDS-RCMD; normal karyotype, IPSS: Int-1) by bone marrow examination. MDS remission was achieved following bone marrow transplantation from an unrelated donor, and he is currently alive without relapse. The patient's father had also been diagnosed with MDS when he was young and died from leukoencephalopathy at approximately 50 years old. These observations support a diagnosis of familial MDS. GATA2 mutation p.R230Hfs * 44 was identified in both bone marrow and control cells (buccal swab) at MDS diagnosis, and he was diagnosed with monocytopenia and mycobacterial infection (MonoMAC) syndrome. Furthermore, an acquired STAG2 mutation (splicing site change, c.820-2A>G) in the bone marrow cells was also identified, which might contribute to MDS progression.

Mesenchymal stem cells (MSCs) have received considerable attention in allogeneic hematopoietic cell transplantation because of their abilities to modulate immune responses and promote hematopoiesis. Because MSCs are capable of producing several cytokines and growth factors, they have been widely used in the treatment of graft-versus-host disease (GVHD). A number of clinical trials have demonstrated the safety and efficacy of MSC therapy for acute GVHD. Moreover, in Japan, allogeneic bone marrow-derived MSC product, TEMCELL ® , was approved as a regenerative medicine for acute GVHD. Besides, MSCs can also produce bone marrow stroma and promote hematopoiesis, the co-transplantation of hematopoietic stem cells and MSCs have been efficiently performed in cord blood transplantation and HLA-mismatched transplantation to enhance engraftment and prevent GVHD. In this review, we provide an overview of clinical trials using MSCs in allogeneic hematopoietic cell transplantation and discuss the possibilities and optimization of MSC therapy.

Documentation of the current status of specialty training to become a neurologist in Japan would represent an important basis for constructing better neurology training program in the planned reform of the specialty training system in Japan. The committee for future neurology specialty system of Japanese Society of Neurology (JSN) conducted a questionnaire survey on the process of specialty training of each trainee for neurology in board-certified educational facilities and semi-educational facilities throughout Japan. The response rate was 46.2% in all facilities and 87.5% in medical universities. The training process of 905 trainees over 5 grades was clarified, which was estimated to be about 80% of all the relevant subjects. Specialty training dedicated to neurology was started at the 3rd year of residency in 87.8% of subjects. During the 3 years following junior residency, 51.3% of subjects ran the rotation training between university and city hospital, whereas 36.5% was trained within the same institution throughout the 3 years of training period.

We report a 62-year-old woman with a history of Basedow's disease and Sjogren's syndrome who presented with slowly progressive limb muscle weakness over the course of ten years. On physical examination, she had dry eye and mouth, but was otherwise normal. Neurological examination revealed symmetrical proximal dominant muscle weakness. Polymyositis was suspected at initial diagnosis due to her clinical course, physical examination, and autoimmune disease. However, the final diagnosis based on a muscle biopsy was the chronic myopathic type of sarcoid myopathy. Among 25 definite sarcoid myopathy cases in the National Center of Neurology and Psychiatry muscle repository from 2010 to 2015, 6/25 had autoimmune diseases. All 6 patients were female and had the chronic myopathic type of sarcoid myopathy. The number of patients with Sjogren's syndrome, thyroid disease, autoimmune hepatitis, and idiopathic thrombocytopenia were 4, 1, 1, and 1, respectively. Only the present case had both thyroid disease and Sjogren's syndrome. In conclusion, the chronic myopathic type of sarcoid myopathy is one possibility to consider in patients who present with progressive myopathy together with autoimmune diseases.

Unlike in Western countries, chronic lymphocytic leukemia (CLL) is a rare lymphoid malignancy in Japan, and its clinical features remain to be elucidated in the Japanese population. Therefore, we retrospectively analyzed 29 Japanese CLL patients newly diagnosed at our institute. Seventeen (59%) were male, and their median age was 62 years. With a median follow-up period from diagnosis of 69 months (range, 3-170 months), 9 patients received some form of treatment for CLL. Three patients died of disease progression with or without infection (n=2) or skin cancer (n=1). Five-year overall and treatment-free survival rates were 83% (95%CI, 46-96%) and 67% (95%CI, 45-81%), respectively. Two patients received allogeneic hematopoietic stem cell transplantation for refractory disease, and both were alive without disease relapse at 53 and 110 months, respectively, after transplantation. These results suggest the clinical courses of Japanese patients with CLL to be comparable to those in Western countries. However, future studies of larger numbers of patients are needed to further elucidate the features and long-term clinical courses of CLL in the Japanese population.

Presently we, Keio Endocrine and Metabolite Survey (KEMS) study group conducted a questionnaire sur- vey with respect to panic values in the laboratories belonging to Keio University-associated hospitals. As to the initial setting, most of the laboratories answered to play a leading role in preparing the necessary matters to implementation of panic values and revise them corresponding to physician's request on each occasion. In almost all laboratories, they did not verify whether the notification procedure does work to exert appropriate clinical action. The numbers of critical values answered by the 18 laboratories distributed widely in the test items (8-39) and their critical limits (10-68). As to the critical limits, the lower limits of serum K and blood glucose converged among the laboratories, however, the limits of other test items diverged. The results of the present survey regarding to critical values, although being in small scale, may submit the im- portant issue to be solved in near future. [Short Communication].

Mohs paste is an external preparation containing zinc hydrochloride and zinc oxide starch as the main ingredient, and it is used for the palliative treatment of patients with surgically untreatable malignant tumors. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. To overcome these problems, we modified the formulation of Mohs paste by excluding starch, which is the cause of physical changes, and investigated the base. In the modified Mohs paste using the macrogol ointment for the base, no marked change with time was noted in the hardness, malleability, or elongation property, and the water-absorbing properties were equivalent to those of Mohs paste immediately after preparation. The hardness did not decrease even after absorbing water. The drug release rate increased 1.5 times with the modified Mohs paste. Based on these findings, the risk of liquefaction-associated damage of the surrounding skin decreased on using the modified Mohs paste, and preparing in advance became possible. These results suggest that the modified Mohs paste using the macrogol ointment for the base exhibits an equivalent effect for control of exudate and a high effect for tissue fixation.

Pathological changes of Parkinson's disease begin before the advent of motor symptoms. At the onset of Parkinson's disease (PD), already half of dopaminergic neurons are degenerated. It is useful to reveal the time course in the prodromal PD in order to establish the early diagnosis markers and the modifying therapies for PD. The Japan Parkinson's Progression Markers Initiative (J-PPMI) is longitudinal, multi-center study to assess the progression of clinical features, imaging and biological markers in the prodromal phase of synucleinopathy (PD, Lewy body dementia and multiple system atrophy). Subjects of J-PPMI are patients with the rapid eye movement sleep behavior disorder (RBD) which is known as a high risk factor for the development of Parkinson's disease.

Malignant lymphoma with cardiac involvement is difficult to diagnose and treatment selection decisions can be challenging, because patients usually present with atypical disease involvement and the incidence is low. Herein, we describe the clinical characteristics and courses of three non-Hodgkin lymphoma patients showing cardiac involvement. All three patients were male, ages 32, 74 and 64 years. All three patients had presented with cardiac involvement mainly in the right heart system. We promptly performed needle biopsies for patients 1 and 3, and open-heart biopsy for patient 2, which showed PMBL for patient 1, DLBCL for patients 2 and 3. Since we were concerned regarding possible transient exacerbation of heart failure or the occurrence of fatal arrhythmia, we chose to start with relatively low dose chemotherapeutic interventions or pre-phase steroid therapy. After one course of chemotherapy or pre-phase steroid therapy, symptoms associated with heart failure almost completely subsided, and we further administered full-dose chemotherapy thereafter, resulting in complete responses in 2 cases. This case series demonstrates that malignant lymphoma with cardiac involvement is a treatable disease, despite widespread involvement. Furthermore, rapid and appropriate diagnostic imaging and biopsy are important when this disease is suspected.

The number of reported cases of infections due to Capnocytophaga species (spp.) is limited. We herein describe four cases developing bacteremia due to Capnocytophaga spp. during neutropenia after chemotherapy for hematological malignancies. At the onset of bacteremia, 3 of the 4 patients had oral mucositis, and 2 were co-infected with other bacteria. Two patients developed bacteremia while receiving fluoroquinolone as prophylaxis against bacterial infection. Bacteremia resolved with administration of antimicrobial agents in all patients and no recurrences were observed thereafter. The emergence of fluoroquinolone-resistant or beta-lactamase-producing Capnocytophaga spp. has recently been reported. Therefore, Capnocytophaga spp. could be causative pathogens in breakthrough and refractory infections under fluoroquinolone prophylaxis and empiric therapy, respectively, for febrile neutropenia. Capnocytophaga spp. should be recognized as one of the causative pathogens of febrile neutropenia. Furthermore, accumulation of cases and susceptibility data are required to establish an optimal treatment protocol.

A 73-year-old woman was diagnosed with gall bladder cancer by contrast enhanced CT images.The tumor was detected at the fundus of the gall bladder and enhanced heterogeneously.She underwent radical cholecystectomy including Japanese D2 lymph node dissection for gall bladder cancer.After 4 courses of oral S-1(80mg/m2 administered for 4 weeks and then stopped for 2 weeks)as adjuvant chemotherapy, a liver metastasis at segment 5 appeared 11 months postoperatively.It showed a ring enhanced tumor on contrast enhanced CT images.FDG accumulated in a similar lesion on PET-CT images.The patient successfully underwent partial hepatectomy of segment 5 of the liver.However, another liver metastasis at segment 7 appeared 5 months after the second operation, but it was resected successfully.The primary lesion and both liver metastases showed similar microscopic appearances.Seven courses of gemcitabine therapy(gemcitabine 1,000mg/m2 once every week for 3 weeks and then stopped for 1 week)were administered as adjuvant chemotherapy.She is now doing well without any sign of recurrence 2 years after the initial operation and 14 months after the secondary liver resection.

Sporadic late onset nemaline myopathy (SLONM) associated with monoclonal gammopathy of undetermined significance (MGUS) is an adult onset myopathy with poor clinical outcomes, requiring high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM-SCT). Here we report two cases of SLONM associated with MGUS in which improvements were achieved only with immunotherapy. A 39-year-old woman had a two-year history of dropped head syndrome and progressive proximal weakness. On admission, she was able to walk with assistance and had lordosis with camptocormia. Combination therapy with plasmapheresis and intravenous immunoglobulin in addition to intravenous methylprednisolone pulse therapy ameliorated camptocormia and proximal weakness after one year. A 51-year-old man had difficulty in raising his arms and required walking assistance prior to visiting our hospital. He had proximal weakness and atrophy, winged scapulae, and gait disturbance. After combination immunotherapy, no progression was observed for 13 years. In both cases, patients did not desire to undergo HDM-SCT, and IgG kappa monoclonal protein was positive, of which the levels were normalized after immunotherapy. Combination immunotherapy can be a possible alternative to HDM-SCT in patients with SLONM. Both patients showed myogenic changes with abundant fibrillation, and needle EMG revealed positive sharp waves. Case 1 showed high signal intensities in MRI STIR/T2WI in muscles showing weakness. These findings are commonly observed in patients with myositis, suggesting that, without muscle biopsy, SLONM may be misdiagnosed as myositis. Muscle biopsy revealed scattered fibers with nemaline bodies without type 2B deficiency, which are important pathological findings that differentiate SLONM from congenital nemaline myopathy.

A large-scale patient survey was conducted in 2013 and results compared with those of a similar scale survey conducted in 2008 to clarify the current status of drug therapy and patients' understanding of Parkinson disease (PD) and therapy. A total of 4,278 and 101 patients respectively participated in primary mail survey and secondary interview surveys. Measures of PD severity, activity level, and level of assistance required in daily life were improved compared with those in the 2008 survey. Average daily dose of levodopa was increased across all disease durations. The treatment compliance rate of monoamine oxidase-B inhibitors was increased in patients with < 6 years of disease duration, but was reduced in patients with ≥ 6 years. The treatment compliance rates of catechol-O-methyltransferase inhibitors and zonisamide were increased. Patients with experience of dyskinesia hoped more to improve their mobility rather than avoid dyskinesia. Since there is no fundamental treatment for PD and drug therapy achieves only symptomatic relief, PD exerted a negative influence on patients' satisfaction. The patients' unsatisfied feelings changed with the severity of OFF time. Physicians are required to not only devise a selection and dosage of PD therapeutic drugs but also empathetically respond to patients, with consideration of their feelings. (Received January 22, 2016; Accepted April 11, 2016; Published September 1, 2016).

The accurate and standardized diagnosis of cytomegalovirus (CMV) infection is important for immunocom- promised patients. We prospectively evaluated the performance of an automated and standardized real-time polymerase chain reaction (PCR) -based DNA quantification for the detection of CMV. The results of PCR- based analysis were also compared with pp65 antigenemia (Ag) assay in the clinical records. The PCR- based analysis of 144 plasma samples from 26 patients with hematologic diseases detected CMV in 69 (48.0%) samples (range, <150-1.28 X 10⁴ copies/mL) while Ag detected CMV in 32(22.2%) samples (range, 1-37/50,000 cells). The number of concordant samples between the two tests was 95(66.0%). There were nine patients who had an Ag-positive period sandwiched by Ag-negative periods and, in all these patients, the Ag-positive period was completely covered by PCR-positive period. These results suggest that PCR can detect CMV more sensitively than Ag. The automated and standardized PCR for detection of CMV can support the appropriate management in patients with risks of CMV infection. [Original].

A direct thrombin inhibitor (DTI), dabigatran was expected to be available for therapeutic use without mon- itoring. However, a number of severe bleedings occurring in patients on medication with dabigatran have been reported. The impact of dabigatran concentrations on major bleeding risk has also been revealed. Therefore, the significance of monitoring of dabigatran is of considerable interest. Hemoclot thrombin inhib- itor assay enables quantification of dabigatran concentrations but is not yet routinely available for clinical la- boratories in Japan. Based on spiking experiments with another DTI, argatroban, we previously demon- strated that the discrepancy in resulting quantification of fibrinogen concentrations between two different thrombin concentrations used in the Clauss assay may enable monitoring of DTIs. In the present study, analogous experiments using dabigatran were carried out, providing similar findings. The measured values of fibrinogen in the presence of dabigatran were similar to those in the absence of dabigatran when assayed using the high thrombin concentration (high-thrombin). The measured values of fibrinogen decreased in parallel with the increase in dabigatran concentrations when assayed using the low thrombin concentration (low-thrombin). Fibrinogen ratio, which is calculated by dividing the fibrinogen value measured with high- thrombin by that measured with low-thrombin, increased more sensitively at the high range of dabigatran concentrations than at the low range. Our observations suggest that the fibrinogen measurement based on the Clauss assay is practically applicable to monitoring of dabigatran especially for prediction of the bleeding risk. [Original].

Dopamine transporter (DaT) single-photon emission computed tomography (SPECT) and [18F]fluoro-L-DOPA ([18F]DOPA) positron emission tomography (PET) facilitate the investigation of dopaminergic hypofunction in neurodegenerative diseases. DaT SPECT and [18F]DOPA PET have been adopted as survey tools in clinical trials. In a large study on Parkinson's disease, 4-15% of subjects clinically diagnosed with early-stage Parkinson's disease had normal dopaminergic functional imaging scans. These are called Scans without Evidence of Dopamine Deficit (SWEDDs), and are considered to represent a state different from Parkinson's disease. Neurological diseases that exhibit parkinsonism and have normal dopaminergic cells in the nigrostriatal system (e.g., essential tremor, psychogenic parkinsonism, DOPA-responsive dystonia, vascular parkinsonism, drug-induced parkinsonism, manganism, brain tumor, myoclonus-dystonia (DYT11), and fragile X syndrome) might be diagnosed with SWEDDs. True bradykinesia with fatigue or decrement may be useful for distinguishing between Parkinson's disease and SWEDDs. However, because SWEDDs encompass many diseases, their properties may not be uniform. In this review, we discuss DaT SPECT, the concept of SWEDDs, and differential diagnosis.

Methylprednisolone administered at a dose of 2 mg/kg is a standard first-line systemic therapy for grade II to IV acute graft-versus-host disease (GVHD). Lower dose methylprednisolone or prednisone, at doses of 0.5-1.0 mg/kg, is also accepted as a first-line therapy for mild acute GVHD. Response rates of grade II to IV acute GVHD to systemic corticosteroid therapy in Japanese patients range from 40-70%, depending on the donors. No improvement within 5 days after first-line therapy or progression within 3 days after first-line therapy could make patients eligible for second-line treatment. However, due to there being few treatment options for steroid-resistant acute GVHD, decisions to initiate second-line treatment are on occasion made 2-3 weeks after first-line therapy in Japan. Previous studies do not support the choice of any specific agent for second-line treatment of acute GVHD. Anti-thymocyte globulin and mesenchymal stem cells are covered by health insurance in Japan. Establishment of new evidence for GVHD treatment is required.

We encountered a case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy for a long time. A pancreaticoduodenectomy was successfully performed on an 80- year-old man. Multiple liver metastases developed 6 months postoperatively. Microscopically, the primary lesion was diagnosed as adenosquamous carcinoma with anaplastic carcinoma component, and the final diagnosis was considered to be Stage Ⅲ disease. S-1monotherapy (80 mg/day, administered for 4 weeks and then stopped for 2-weeks) was effective. A partial response was noted after 3 months, and 9 months after the initial administration of S-1, a complete response was achieved, which persisted for more than 12 months, according to contrast-enhanced CT evaluations.Serum CEA and CA19-9 levels, which became slightly elevated at the time of liver metastasis development, normalized promptly and remained within normal limits. Adverse effects of chemotherapy of more than grade 2 severity were not apparent, and the patient tolerated the 11th course of S-1 administration, consistently. A standard therapeutic strategy and its outcomes in cases of pancreatic cancer recurrence are not clearly outlined in the Japanese Guideline for the Treatment of Pancreatic Cancer. A case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy is reported in this paper.

A 60-year-old man underwent total gastrectomy with Japanese D2 lymph node dissection for advanced gastric cancer. The resected specimen was diagnosed as well-differentiated tubular carcinoma, pT3, pN1, cM0, and the final stage was considered as ⅡB. During adjuvant chemotherapy with S-1 (120 mg/day, administered for 4 weeks and then stopped for 2 weeks), multiple liver metastases were detected by contrast-enhanced CT images 6 months after the operation. Eight courses of XP therapy (capecitabine 1,600 mg/m2/day: day 1-14, cisplatin 70 mg/m2/day: day 1, then stopped until days 15-21) were administered in consideration of the recurrence during adjuvant chemotherapy with S-1, resulting in a partial response. Adverse events such as grade 1-2 abdominal pain, general fatigue, and the resultant deterioration of ADL led to discontinuation of chemotherapy. The residual liver metastasis was treated with RFA therapy, causing it to disappear completely. Serum CEA level was 5.5 ng/mL postoperatively, elevated to 13.9 ng/mL at the time of recurrence and 2.4 ng/mL after XP and RFA therapy. He is doing well without any recurrence 2 years and 6 months later.

A 47-year-old man visited our hospital with complaints of abdominal pain and hematuria.He was diagnosed with unresectable rectal cancer invading the urinary bladder with multiple liver metastases. Systemic chemotherapy with mFOLFOX6 and panitumumab was started soon after sigmoid colostomy. Three months later, both the primary tumor and the liver metastases had partially responded. Another 2 months later, he complained of terrible abdominal pain. CT images revealed a huge primary tumor and hemorrhage in the sigmoid mesocolon occupying the pelvic cavity. A salvage operation was performed and the primary tumor was palliatively resected. Soon after the operation, a local recurrence appeared and grew rapidly. He died 8 months after diagnosis. Rapid growth of the primary tumor seemed a limiting factor for the prognosis.

Laparoscopy-assisted low anterior resection (Japanese D3 lymph node dissection) was performed to treat a 68-year-old man for rectal cancer. Microscopically, the resected specimen was diagnosed as a moderately differentiated adenocarcinoma and the final stage was considered as pT3, pN1, cM0, pStage Ⅲa. He was administered capecitabine for 6 months as adjuvant chemotherapy. Then, enlarged para-aortic lymph nodes, indicated by follow up CT at 1 year and 11 months postoperatively developed behind the left renal artery. FDG accumulated in it, consistent with the CT images. Para-aortic lymph node dissection was performed after the diagnosis of solitary lymph node metastases. Microscopically, the resected lymph nodes showed features similar to the primary lesion. He is doing well without recurrence for 4 year and 6 months, without any adjuvant chemotherapy. Para-aortic lymph node metastases are frequently associated with other distant metastases; if not, a complete cure may be possible by curative resection for solitary metastases.

Graft-versus-host disease (GVHD) is an important complication in allogeneic hematopoietic stem cell transplantation. The standard regimen for GVHD prophylaxis in bone marrow transplantation and peripheral blood stem cell transplantation from human leukocyte antigen-matched donors is a combination of a calcineurin inhibitor, such as cyclosporin or tacrolimus, and short-term methotrexate. This regimen is well researched and has been nearly optimized in terms of infusion methods and the target blood concentration. The use of mycophenolate mofetil instead of methotrexate has the advantage of a lower incidence and severity of oropharyngeal mucositis. The addition of anti-thymocyte globulin significantly decreases the incidences of severe acute GVHD and extensive chronic GVHD, but does not lead to a significant improvement in overall survival. The GVHD prophylaxis regimens in cord blood transplantation and HLA-haploidentical donor transplantation have not been standardized. The efficacy of other immunosuppressive drugs, regulatory T lymphocytes, and mesenchymal stem cells are currently under investigation. Establishment of new evidence for GVHD prophylaxis from Japan is expected.

Hepatitis B virus (HBV) infection is a global public health problem. HBV has been classified into eight genotypes (A to H) based on complete nucleotide sequencing. The prevalence of specific genotype varies geographically. The rationale for treatment in patients with chronic hepatitis B is to reduce the risk of progressive chronic liver disease, such as cirrhosis and hepatocellular carcinoma. Treatment strategies for chronic HBV infection include interferon and nucleotide analogues (lamivudine, adefovir dipivoxil, entecavir, and tenofovir disoproxil). HBV persists in the body even after serological recovery from acute hepatitis B. Thus, individuals who have been exposed to HBV are at risk of the reactivation of infection, which may result in an increase in serum aminotransferases or a flare when the immune response is suppressed. Patients requiring immunosuppressive therapy should undergo serologic testing for markers of HBV infection. This topic review summarizes these issues related to the management of hepatitis B.

Venous thromboembolism is a multifactorial disease resulting from complex interactions among genetic and environmental factors. To date, numerous genetic defects have been found in families with hereditary thrombophilia, but there may still be many undiscovered causative gene mutations. We investigated a possible causative gene defect in a large Japanese family with inherited thrombophilia, and found a novel missense mutation in the prothrombin gene (p.Arg596Leu) resulting in a variant prothrombin (prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild type prothrombin in clotting assays, but formation of the thrombin-antithrombin (TAT) complex was substantially impaired resulting in prolonged thrombin activity. A thrombin generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis. We also showed the effects of the prothrombin Yukuhashi mutation on the thrombomodulin-protein C anticoagulation system, recent development of a laboratory test detecting antithrombin resistance in plasma, and another antithrombin resistant mutation found in other thrombophilia families.

The number of reported cases of bacteremia due to Rothia mucilaginosa (R. mucilaginosa), a component of the normal flora of human gastrointestinal tract mucosa, is limited. We encountered three cases of bacteremia due to R. mucilaginosa during neutropenia after chemotherapy for myeloid malignancies. Although all three patients were successfully treated with antimicrobial agents, one patient developed disseminated lesions in the lungs and soft tissue. The portal of R. mucilaginosa bacteremia is reportedly mucositis or dental disorders; however, no such complications were identified in our patients. Even in the absence of a preexisting portal, R. mucilaginosa should be recognized as a potential causative pathogen of bacteremia during neutropenic periods. Accumulations of cases and isolates are required to further elucidate the risk factors for developing R. mucilaginosa bacteremia, its clinical course, and the optimal antimicrobial treatment.

A 70-year-old man with an ascending aortic aneurysm was referred to our hospital. He had not shown any head symptoms and blood tests did not indicate any inflammation. Ascending aortic replacement was performed under cardiopulmonary bypass. Pathologic examination of the aneurysm wall was diagnosed for giant cell arteritis( GCA). Aortic aneurysm due to GCA without no symptom was extremely rare.

Thrombocytopenia in patients with chronic hepatitis C represents an obstacle for the initiation of antiviral treatment. Antiviral treatment with pegylated interferon α and ribavirin has contributed to a significant increase in the rate of sustained virological response. However, patients with thrombocytopenia is ineligible for antiviral treatment or, if able to start treatment, may require a dose reduction or even discontinuation due to the haematological adverse effects. We here review the efficacy and safety of antiviral treatment after splenectomy and partial splenic embolization, and the potential effect of platelet count increase by interferon β.

The interaction of warfarin and vitamin K is a clinically significant issue. This study investigated the acceptable intake level of vitamin K among warfarin users by means of a systematic review. We searched two databases (PubMed and "Igaku chuo zasshi")for articles about adverse events arising from interaction of warfarin and vitamin K, published until October 2014. Of 1,310 citations retrieved, 16 studies met the selection criteria for examination of the upper limit, and 6 studies dealt with amounts below the limit. The intake of vitamin K in warfarin patients was acceptable in the range of 25-325 μg/day, with a maximum daily variation of 292 μg, and a value of 150 μg/day seemed optimum. When these results were applied to usual foods, except for dietary supplements or health foods, the only prohibited foods were fermented soybean (natto) and foods containing it, while green leafy vegetables could be acceptable if their intake is limited.

In 2010, "A investigating board of the team medical care" started. In 2011, Nurse Practitioner performing a specific medical practice was discussed in the promotion board of the team medical care. In 2012, the trial of Japan Nurse Practitioner (JNP) was started in NHO hospitals, and one JNP assigned to Takasaki General Medical Center. She received on-the-job training in the division of thoracic surgery. Through the thoracic operation, she gradually acquired many surgical maneuvers, such as thoracotomy and closure chest, insertion of thoracic drainage tube and perioperative management. During two years, she engaged many medical practices, including 180 cases of operative assistances, 160 cases of insertion of thoracic drainage tube.

An 84-year-old woman presented with the chief complaint of melena. Colonoscopy revealed a type 2 tumor that circumferentially occupied the lumen of the lower rectum about 6 cm from the anal verge. A biopsy specimen was obtained from the tumor and the patient was diagnosed with moderately differentiated adenocarcinoma. Computed tomography revealed that the rectal cancer had invaded the marginal fatty tissue, accompanied by several regional lymph node metastases with no distant metastasis. On the basis of this evidence, the tumor was staged as cT4a, cN2b, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative radiotherapy combined with an oral chemopreventive agent (RT 1.8 Gy × 25 frames; total 45 Gy, S-1 80 mg/day) was administered with trivial adverse effects. Laparoscopy-assisted low anterior resection with Japanese D3 dissection was performed successfully. The patient is doing well without recurrence after 14 months of surgery. Histological examination revealed that both the primary lesion and regional lymph nodes had no residual cancer; that is, the histological effect of the preoperative chemoradiotherapy was a pathologically complete response (pCR).

A 71-year-old man presented with sigmoid colon cancer and multiple unresectable liver metastases. As the sigmoid colon cancer caused anemia, we performed laparoscopic-assisted sigmoidectomy prior to the administration of systemic chemotherapy. Bevacizumab (Bv) plus modified Leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) was administered as first line therapy.At 3 months from the start of chemotherapy, computed tomography revealed that the size of the liver metastases reduced by 49.45%, as evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). The only adverse event observed was Grade 1 peripheral neuropathy after the eighth dose of oxaliplatin.As the progression of peripheral neuropathy was observed at the ninth dose of oxaliplatin, oxaliplatin was omitted from further therapy; the patient was converted to maintenance therapy with simplified biweekly Leucovorin and fluorouracil (sLV5FU2). Bv plus mFOLFOX6 followed by sLV5FU2 for first-line therapy was effective for disease management over 23 months, but a partial response (PR) was the best overall response achieved.

The Japanese Society of Laboratory Medicine and Japanese Association of Medical Technologists symposium was held at the 60th National Congress of the Japanese Society of Laboratory Medicine. The theme of this symposium was "What should we do in the Department of Clinical Laboratory in the future?" In this symposium, we discussed the future of the Department of Clinical Laboratory. Three speakers talked about this theme: a laboratory doctor, a laboratory technician, and a laboratory technician training school teacher. The speed and accuracy of routine laboratory work and delivery of the results to medical staff have been evaluated. It is important for medical technologists to improve their ability to estimate laboratory data based on anatomical, pathological, and physiological knowledge. Medical technologists receive many requests. We have to respond to the questions from medical staff and provide patients with appropriate explanations. Our objective is to educate human resources who can support the overall process. We maintain the environment, and nurture various personnel who work in clinical, research, educational, and industrial fields. It is very important for medical technologists to perform their duties as medical staff. Medical technologists contribute to patients' diagnoses and treatments and they participate in hospital administration. Mutual cooperation within the clinical laboratory group may be necessary for future activity.

The point-of-care testing (POCT) has been widely performed as decentralized laboratory testing at the site of patient care. Antsense ROSE (ROSE), a POCT device for measurement of blood glucose, is handheld and time-saving and reduces risks of infection because disposable tips are used. In this study, we evaluated the testing performance of ROSE. This study was approved by the ethics committee of Nagasaki University Graduate School of Biomedical Sciences. Clinical blood samples were used for evaluating the reproducibility of testing, the calibration stability, the linearity of dilution, and the effects of dissolved oxygen partial pressure hematocrit, coexisting materials, and anticoagulant agents on the results of ROSE. Blood glucose values during 75g oral glucose tolerance testing (OGTT) were measured for analysis of the differences between sites of blood collection. Comparing with the automatic analyzer based on the hexokinase assay, the accuracy of blood glucose values measured by ROSE was evaluated. ROSE showed good performances in reproducibility, calibration stability, and dilution linearity. The values measured by ROSE were stable to oxygen partial pressure, hematocrit, coexisting materials, and anticoagulant agents and were correlated with those by the automatic analyzer. The values in capillary blood obtained from the ear or the finger elevated as approximately 30-70% as those in venous blood, at 0.5 and 1 hour after OGTT. The inhibitory effect by sodium fluoride (NaF) was 5-25% decrease after 24 hours. In conclusion, ROSE provides the blood glucose values accurately and is a rapid and useful device as a POCT.

A 64-year-old man underwent kidney transplantation for progressive chronic renal failure which had developed 8 years after allogeneic bone marrow transplantation for acute myeloid leukemia. Because of post-operative complications, he had been placed on intravenous hyperalimentation. Three months after the transplantation, anemia rapidly progressed (hemoglobin, 7.9 g/dl). The proportion of reticulocytes was 0.2%, but white blood cell and platelet counts remained within normal ranges. Serum iron, vitamin B12, and folate levels were normal. Bone marrow examination showed the presence of ringed sideroblasts and cytoplasmic vacuoles in a fraction of erythroid cells. Megakaryocytes were adequate in number with normal morphology. Although the findings were consistent with refractory anemia with ringed sideroblasts according to the WHO classification, cytoplasmic vacuolations were also observed in myeloid cells, suggesting copper deficiency. Indeed, serum copper and ceruloplasmin levels were found to be low (33 μg/dl and 11 mg/dl, respectively), and oral copper supplementation at a daily dose of 1 mg was initiated. There was a prompt increase in reticulocytes, and the hemoglobin level was normalized within one month, in response to this regimen. In progressive anemia cases with ringed sideroblasts in the bone marrow, copper deficiency should be considered in the differential diagnosis.