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For the analysis of nitrite ions in food, the stabilities of nitrite ions in meat products and their standard solutions were evaluated. Nitrite is easily oxidized or reduced; hence, products with standard solutions or colour retention agent must be carefully handled. To assess the stability and decreasing trend of nitrite, we examined the storage stability of standard solutions using calibration curves, the time course of nitrite in chopped meat products stored under different conditions, and the time course of nitrite in the sample solutions. Regarding calibration curves, the storage stability was determined for standard solutions that were prepared with ultrapure water at concentrations of 0.025 and 0.4 μg/mL and were stored at 5℃ for one year. The results revealed no changes in concentration of any solution over time, suggesting that no readjustments to the standard solution concentration were necessary before testing until one year after their preparation. Time course of nitrite in chopped meat products stored under different conditions showed a significant decrease in nitrite in refrigerated storage (5℃), whereas stability of nitrite was maintained for up to 1 day in frozen storage (-20℃) and for 14 days in frozen storage (-40℃). The time course of nitrite in the sample solutions showed that the quantitative values of nitrite in the extract remained unchanged within one week of extraction for the meat products tested in the study.

We report with the addition of literature because we have experienced 3 cases of locally advanced breast cancer with skin invasion that have alleviated symptoms and improved quality of life by using Mohs paste. In Case 1, Mohs paste reduced exposed tumors, exudation, and bleeding. In Case 2, bleeding, which had been the cause of the marked anemia, was controlled, and tumor shrinkage and epithelialization were observed. Case 3 had a poor prognosis due to systemic metastasis, but the QOL improved for a certain period of time as exudation, bleeding, and foul odor were controlled. From the viewpoint of palliative care, Mohs paste is a safe and effective treatment method against various symptoms such as large amounts of exudation, bleeding, and foul odor caused by breast cancer skin invasion, and depending on the case, prognosis can be expected to be extended by shrinking the tumor. The cooperation of not only doctors but also palliative care teams including pharmacists and nurses is essential for use.

A 49-year-old woman presented with abdominal pain. A computed tomography scan revealed a left breast mass with suspected peritoneal dissemination. She had no notable family history of the disease. Following a detailed examination, she was diagnosed with ovarian cancer(Stage ⅢC)and left breast cancer(Stage Ⅰ). After confirming the diagnosis of ovarian cancer with a laparoscopic biopsy, neoadjuvant chemotherapy was scheduled. Due to its efficiency in reducing tumor burden, debulking surgery was also performed. While receiving adjuvant chemotherapy for ovarian cancer, concomitant anastrozole was administered for breast cancer. A pathogenic variant of BRCA2 was subsequently identified. Once adjuvant chemotherapy for ovarian cancer had been completed, a left mastectomy and sentinel lymph node biopsy were performed as management for breast cancer. The patient will continue treatment with anastrozole for breast cancer and olaparib for ovarian cancer and will be followed up appropriately.

Superficial temporal artery-middle cerebral artery(STA-MCA)bypass surgery is necessary for vascular reconstruction in patients with hemodynamic ischemia, including moyamoya disease and complex aneurysms. This report introduces the fundamental techniques of STA-MCA bypass surgery practiced in my institute. Preoperative and perioperative management is important to minimize complications. During the procedure, the operator should keep a bloodless surgical field to facilitate the bypass. The vascular lumen and intima must be carefully observed during anastomosis, especially in moyamoya cases. In addition, this study emphasizes the importance of off-the-job training using animal or synthetic arteries because this technique includes special movements compared with that of other microsurgical procedures.

In Japan, the medical fee revision in April 2018 allowed insurance coverage for robot-assisted cardiac surgery for mitral and tricuspid valve plasty. We started robot-assisted mitral valve plasty by da Vinci system in June 2019. The artificial chordae reconstruction by the loop method, which has been our basic surgical technique so far, has also been adopted in robot-assisted cardiac surgery. The author has performed three dimensional( 3D) endoscopic minimally invasive cardiac surgery( MICS), but now focuses on robot-assisted cardiac surgery because of the delicate procedure and good operability. The venous drainage cannulation through the femoral vein is done under fluoroscopy. We use a silicon cylinder, that is elastic and provides a wide field of view, to approach to the papillary muscle. Robot-assisted cardiac surgery, which takes a little longer than through a mid-sternum incision, requires some ingenuity to save time. We also mention cadaver training that had to be experienced abroad, such as robot training with a human body donation that will start soon at our hospital.

The continence self-management programme fee (CSPF) for hospitalized patients was revised in 2020 to include those receiving consistent care on an out-patient basis. We extracted candidate patients for CSPF on an out-patient basis (out-patient candidates hereafter) from those for whom-CSPF had been calculated during hospitalization at our hospital, and defined those who had undergone a medical examination related to continence care as out-patient calculation candidates. Of the 956 patients for whom CSPF had been calculated during hospitalization, 482 patients (50%) were out-patient candidates ; 275 (54%) and 169 (33%) of whom were seen in the urology and neurosurgery departments, respectively. Of the 482 out-patient candidates, 238 (49%) were out-patient calculation candidates ; 197 (83%) and 14 (6%) of whom were seen in the urology and neurosurgery departments, respectively. Forty-two and 41 of the calculation candidates were cases of benign prostatic hyperplasia and bladder cancer, respectively. The CSPF was actually processed 93 times for 78 of the 482 out-patient candidates (16%). There were various obstacles in the current system of calculating the fees to realize consistent care from hospitalization to out-patient care.

In this study, we simultaneously determined three antioxidants, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and tert-butylhydroquinone (TBHQ), using HPLC equipped both with a photodiode array detector and a fluorescence detector in 25 minutes per sample. Due to the combined use of the two detectors, we could achieve improved target selectivity. Further, quantification at the specific wavelengths for each target substance particularly increased BHT detection sensitivity. This approach enabled us to avoid repeated measurements during daily inspections. Furthermore, detections were performed using LC-MS/MS instead of GC-MS to overcome the problem of helium gas shortage.In addition, we investigated antioxidant stability in standard solutions during storage. Although TBHQ was stable in methanol with ascorbic acid at -20℃, ascorbic acid storage has possibility to lead to decrease in BHT and BHA concentrations. We recognized that the mixture of BHT and BHA dissolved in methanol at 4℃ and that of BHT, BHA and TBHQ dissolved in methanol with ascorbic acid at -20℃ were suitable for about one year.

Recently, a KRAS mutation located in the endothelial cells of the nidus in arteriovenous malformations(AVMs)was reported. The findings indicate the possibility of medical therapy against cerebral AVMs; the blockade of RAS-MAPK signaling cascade may stabilize AVM nidus. As for surgical treatment for AVMs, achievement of low morbidity is the most important objective. To achieve this, assessment of blood flow, usage of non-stick bipolar forceps, and 3D simulation prior to operation are important. Assessment of individual cases for surgical treatment leads to low morbidity in surgeries.

(Purpose) This study examined the usefulness of positron emission tomography (PET) / computed tomography (CT) in the diagnosis of metastasis in patients with urothelial carcinoma. (Materials and methods) The subjects were patients who were newly diagnosed with urothelial carcinoma in our department on whom we performed CT and PET/CT to search for metastasis. (Results) The median age of the 92 subjects was 71 years, and bladder and upper tract urotherial cancer were underlying diseases in 41 (46%) and 51 (54%) patients, respectively. In 66 (72%) of the 92 cases, no metastasis was observed by CT, while PET/CT revealed metastasis in 9 (14%). The 57 (86%) patients in whom both CT and PET/CT showed no metastasis underwent radical surgery, while 2 patients (4%) exhibited pathological lymph node metastasis.Of the 26 patients in whom CT revealed metastasis, PET/CT showed no metastasis in 3 (12%), and the absence of pathological metastasis was confirmed in all patients. Of the 23 patients found to have metastasis in both CT and PET/CT, metastasis that could not be identified by CT was discovered by performing PET/CT in 10 (43%) patients.PET/CT showed significantly higher diagnostic accuracy than CT alone (p< 0.01), with sensitivities of 94.1% and 67.6%, specificities of 100% and 94.8%, and positive diagnosis rates of 97.8% and 84.7%, respectively. (Conclusions) PET/CT in patients with urothelial cancer revealed that metastases that cannot be diagnosed by CT alone are found at a significant frequency. Since these metastases can affect treatment choices in patients with urothelial cancer, PET/CT is considered to be useful in diagnosing patients with urothelial cancer.

A 70-year-old patient who survived about 40 years after left pneumonectomy for tuberculosis visited emergency hospital, because of dyspnea. She received suitable medical therapy for atirial fibrillation and severe mitral regurgitation and hesitated heart surgery because of anxiety for surgical risk. The computed-tomography showed mediastinal shift to left and right lung compensatory expansion. Respiratory function test after treatment of heart failure showed only mild restrictive disorder. And the blood-gas examination in room air was 101 mmHg of Pao2 and 37 mmHg of Paco2. The mitral valve replacement was performed via median sternotomy and using normal cardiopulmonary bypass. And she fully recoverd without any respiratory complications. Mediastinal shift did not obstract the surgical view and establishment of cardiopulmonary bypass in this case. It seemed that the key of surgical successs is the preserved function of healthy residual lung.

An 86-year-old man was referred to our hospital with pulmonary tuberculosis developed during postoperative chemotherapy for gastric cancer. We initiated treatment with an anti-tuberculosis drug. Following confirmation of the effectiveness of this regimen, we combined the treatment with anti-cancer drugs. Tuberculosis treatment was completed without any drug interactions or serious side effects due to multidrug administration. For cancer patients who developed tuberculosis, combination treatment requires careful observation; however, it is a treatment option that can control both diseases.

Neuropathic pain in patients with cancer often do not respond to both opioid and non-opioid analgesics. Tapentadol has two medical effects: action on the μ opioid receptor and inhibition of noradrenaline reuptake; thus, it is expected to be effective for neuropathic pain. We investigated its effect on neuropathic pain in 40 patients with cancer who received tapentadol between June 2017 and May 2020 at the Japanese Red Cross Nagoya Daini Hospital. We compared the level of neuropathic pain using an NRS before and after tapentadol administration. The NRS score(median)decreased from 7 to 4.5 within 15 days after first administration or dose increase(p<0.05). Twenty-two patients(55%)showed more than 33% improvement in the NRS score. These results suggest that tapentadol may contribute to a reduction in neuropathic pain.

This is the case of a 72-year-old man in whom multiple colorectal cancers including rectal and appendiceal cancers and synchronous S3 liver metastases were observed in 2014, and resection was performed in 2 stages. In 2017, a single recurrence was found in the liver S8, and he underwent a liver S8 sub-segmental resection. Implantation of a CV port for postoperative chemotherapy was planned. At the time of insertion, the catheter was punctured from the exterior portion of the left subclavian vein to avoid the pinch-off syndrome wherein the catheter is crushed between the clavicle and the first rib. Subsequently, FOLFOX therapy was started, but it was discontinued because of allergic symptoms, which appeared during the third course. Two years after the CV port was implanted, a catheter fracture was found on a chest X-ray performed during a regular visit. Since the detached catheter did not fall into the vein, it was possible to remove the port under fluoroscopy. When a catheter is implanted, even under ultrasound guidance, it is considered important to always keep in mind the possibility of a catheter fracture and to detect and respond to it early.

We evaluated the impact of tumor shrinkage (TS) induced by molecular targeted therapy as the first-line systemic therapy on the survival of patients with metastatic renal cell carcinoma (mRCC). A total of 67 patients with mRCC who received first-line molecular targeted therapy were included in this study. Sixty patients were evaluable by response evaluation criteria in solid tumors. Patients underwent the first evaluation at 8-12 weeks after the start of the therapy. Twenty patients had TS ≧30%, 32 from 30% to -20%, and 8 ≦-20%. The median overall survival periods of patients who achieved TS ≧30%, from 30% to -20%, and ≦-20% at first evaluation were 41.0, 35.0, and 11.5 months, respectively. Univariate and multivariate analyses showed that TS of≧0%, in addition to negative C-reactive protein and the absence of bone metastasis were good predictors of overall survival. The patients who achieved 0% or more at the initial evaluation had longer survival than those who had no tumor reduction (40.0 months vs 12.0 months, p<0. 001). These findings suggest that early TS affects overall survival in real practice. We should consider alternative therapies for patients who have not achieved tumor reduction at the initial evaluation.

Renal cell carcinoma (RCC) metastasis to the bladder is rare. We report two cases that occurred metachronously during pazopanib treatment for other metastases. To our knowledge, this is the first report to demonstrate bladder metastasis from RCC during molecular targeted therapy with pazopanib. (Case 1) A woman in her 60s was referred to our department for evaluation of an incidental right renal tumor. Dynamic CT showed a 6 cm renal cell carcinoma. In February 201X she underwent laparoscopic right radical nephrectomy, revealing clear cell carcinoma (grade 1>2), stage pT3aN0M0. In February 201X+1 she complained of left pelvic pain. She was found to have metastasis to two iliac bones and an occipital bone. She received pazopanib, in addition to a bone modifying agent and radiotherapy for the iliac bones. After 8 months, she complained of asymptomatic gross hematuria in spite of having stable disease for bone metastasis. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor on the posterior wall. She underwent transurethral resection of bladder tumor (TUR-BT). Histological examination showed metastatic RCC. Thereafter she received sequential therapies (axitinib, sunitinib, nivolumab). She remains alive without recurrence in the bladder 51 months after TUR-BT. (Case 2) A woman in her 60s presented to our department with a complaint of painless gross hematuria. A dynamic CT showed an 8.5 cm renal cell carcinoma and multiple lung metastases. In March 201Y she underwent right radical nephrectomy, revealing clear cell carcinoma (grade 2>3), stage pT2aN0M1. In June 201Y she started pazopanib. After 9 months CT showed a bladder tumor in addition to progression of lung metastases. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor at dome. She underwent TUR-BT. Histological examination showed metastatic RCC. She had no recurrence in the bladder during follow-up although she died of RCC.

When a 74-year-old male patient visited our hospital for the treatment of herpes zoster, his computed tomography (CT) revealed a mass in his right breast, axillary lymph node enlargement, and multiple lung nodules. A histological examination of the breast and lymph node biopsies revealed diffuse large B-cell lymphoma (DLBCL) while the bronchial and salivary gland biopsies showed secondary amyloidosis and Sjögren's syndrome (SjS). According to the Ann Arbor staging, the clinical stage of the lymphoma was evaluated as IIE. The patient achieved a complete remission after six cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) combined with intrathecal chemotherapy to prevent meningeal infiltration and irradiation after chemotherapy. Primary breast lymphoma was diagnosed within 2% of the breast tumor. Only sixteen male cases of breast lymphoma have been previously reported. In those reports, gynecomastia and hormonal therapy accounted for nine cases, but none of the cases coexisted with SjS. The present case is suggestive of the need to investigate possible autoimmune involvement in the development of lymphoma.

Nosocomial coronavirus disease 2019 (COVID-19) had occurred at our hospital. We retrospectively analyzed the differences between patients with nosocomial COVID-19 and either hematological disease (n=40) or other diseases (n=57). The analysis was completed within 60 days for surviving patients. Among the patients with hematological disease and those with other diseases, there were 21 (52.5%) and 20 (35.1%) deaths, respectively. Although the patients with hematological disease received favipiravir more frequently than patients with other diseases (21 [52.5%] vs. 15 [35.3%], respectively; P<0.05), their median overall survival was poor (29 days; P=0.078). Furthermore, the median duration from oxygen therapy initiation to death or intubation was significantly shorter in the patients with hematological disease (5 days [range, 1-17 days] vs. 10 days [1-24 days], respectively; P<0.05). Furthermore, the patients with hematological disease and nosocomial COVID-19 exhibited more marked respiratory failure and poorer outcomes leading to death in a shorter time period than the patients with other diseases and nosocomial COVID-19.

Objectives: We investigated the quality of life (QOL) of patients using the Free/Low-Cost Medical Care Program, which is a system that enables people in financial difficulities to receive treatment free of charge or at a low cost. We also investigated the background charateristics and lifestyle of the patients., Methods: The subjects were 226 outpatients who used the Free/Low-Cost Medical Care Program (use group) and 226 outpatients who did not use the program (non-use group). The method was an anonymous cross-sectional servey by mail. The survey items included basic attributes, health-related QOL (HRQOL), feeling of being poor, lifestyle diseases, lifestyle, and connection with the community., Results: The number of respondants with valid responses was 97 in the use group and 85 in the non-use group. Among the basic attributes, there were a significant differense between the use group and the non-use group in the family structure, type of work, household income, and educational background. The HRQOL scores of the physical and social summary components were significantly lower in the use group than in the non-use group. The HRQOL scores of mental summary component were higher than the national standard HRQOL score in both the use and non-use groups., Conclusions: In this study, it was considered that old age affected the HRQOL scores of the physical and social components. It was considered from the HRQOL scores of the mental aspect that the use of the Free/Low-Cost Medical Care Program might have contributed to mental stability a certain to extent.

We examined the postoperative urinary continence rate, and preoperative and postoperative factors predicting postoperative urinary continence for patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our hospital. In all, 122 patients who received RARP were retrospectively analyzed. All patients answered a questionnaire to evaluate the urinary condition and also had a follow-up period of 6 months or longer after surgery. We defined urinary continence to be the use of 1 pad per day or less, including a safety pad. Membranous urethral length (MUL) was measured using sagittal sections of T1-weighted MRI. Postoperative urinary incontinence rates were 48.7, 72.4, 82.6 and 86.8% at 3, 6, 12 and 24 months after surgery, respectively. MUL was a significant predictive factor of urinary continence at 6 months after surgery (p<0.01). We examined the factors predicting the urinary continence recovery at 6 months after surgery, including only patients who did not obtain urinary continence at 1 month after surgery. Two factors, MUL of 11 mm or longer and two pads per day at 1 month after surgery, were significant predictive factors of urinary continence recovery at 6 months after surgery (P=0.02, P=0.04). Patients who had a long MUL could easily obtain urinary continence after RARP compared to those with a short MUL. Most patients with a long MUL and with use of 2 pads per day at 1 month after surgery could obtain urinary continence at 6 months after surgery, even if they had urinary incontinence at 1 month after surgery.

A 72-year-old man was referred to our hospital for examination of a right adrenal tumor incidentally found by computed tomography for close inspection of lumbago. The computed tomography scan and magnetic resonance imaging showed a 51×54×43 mm solid tumor in the right adrenal region. Endocrinological examinations were within normal limits. Because we could not diagnose his condition due to atypical radiographic findings preoperatively and exclude a malignant tumor, laparoscopic right adrenalectomy was performed. The tumor was histologically diagnosed as ganglioneuroma originating from the right adrenal glands.

This paper presents the case of an 84-year-old man who was referred to the clinic because of decreased appetite and weight loss. He was diagnosed with anemia and white blood cell count reduction by a local doctor. In consideration of blood diseases, he was referred to the hospital to the department of hematology, and laboratory tests revealed a white blood cell count of 4,400/mL, hemoglobin level of 8.0 g/dL, platelet count of 12,800/mL, and high PSA level of 12.895 ng/mL. Cancer cells were found in the bone marrow biopsy and tested negative on PSA immunostaining. PET-CT revealed increased accumulation of FDG in the whole bone marrow. A biopsy of the prostate showed poorly differentiated adenocarcinoma with a Gleason score of 5+5=10 and weakly positive PSA immunostaining. Prostate cancer with carcinomatosis of the bone marrow was diagnosed. He underwent bicalutamide and degarelix treatment. He was alive 12 months after his first visit.

A 60-year-old man presented at our hospital with gross hematuria. He had been treated for nephrotic syndrome with cyclophosphamide and steroids since he was in his 20s. We detected diffuse hemorrhagic cystitis on cystoscopy and diagnosed him with cyclophosphamide-induced hemorrhagic cystitis. He was hospitalized due to clot retention. We treated him with blood transfusion for severe anemia and conducted continuous bladder irrigation. We performed hyperbaric oxygen therapy and transurethral electric coagulation, and increased the steroid dose. However, we could not control the hematuria. Finally, we performed cystectomy, and he is now well without hematuria. Although cystectomy is the final option, it is important to decide it in a timely manner because a delay decreases the quality of life.

A 65-year-old man was admitted to our hospital complaining of general malaise, anorexia and weight loss. A computed tomography(CT)scan showed massive ascites and multiple peritoneal masses. Although adenocarcinoma was suspected based on the cytology of the ascites, we were unable to determine the site of origin. We next performed a laparoscopy and a biopsy of the tumor on the omentum. The laparoscopy showed small, white, hard nodules that were disseminated throughout the abdominalcavity, and histologicaldiagnosis confirmed malignant peritonealmesothel ioma. The patient was administered chemotherapeutic treatment of cisplatin and pemetrexed. After treatment, the ascites decreased; however, tumor regression was not observed. The patient's performance status gradually decreased, and he died on hospital day 104. Prognosis of malignant peritoneal mesothelioma remains poor, and malignant peritoneal mesothelioma should be considered when diagnosing peritoneal tumors.

In 2010s, several opioids became available in Japan, including methadone, tapentadol and hydromorphone. Methadone was approved in September 2012 by Japanese regulatory authority. Since methadone is positioned as so-calledstep 4 opioidin Japan, it must be prescribed as alternative opioid switched from another of 60mg/day or greater equivalent dose of oral morphine. Diversity of pharmacokinetics among individuals and various drug interactions require close monitoring of adverse events. In spite of these cautions, unique characteristics such as inhibiting N-methyl-D-aspartate(NMDA)and in- ducing internalization/degradation of mu-delta opioid receptor heterodimers underline the value of methadone in opioid switching. Tapentadol, a dual-acting opioid which inhibits noradrenaline(norepinephrine)reuptake, was approved in Japan in March 2014. In a double-blind randomized study comparing with oxycodone, tapentadol showed relatively better tolerability. Advantages such as having no active metabolites and minimal drug interactions also ease the administration of tapentadol to the patients with comorbidities. Hydromorphone, approved in March 2017, has a profile similar to morphine. Higher potency than morphine lead to less production of 3-glucronide metabolite(H3G)which accumulates in patients with renal failure and causes neurotoxicity. Because there is no concluding evidence about effect of hydromorphone on dyspnea or tolerability in patients with renal insufficiency, organized studies are still needed. We expect these "new in Japan" opioids contribute to long-term, stable pain control for patients with cancer.

Standardization of the clinical laboratory and compatible clinical data is needed for accurate diagnosis in routine medical practice or medical care. We have many megaEQSPs in Japan, and they suggest the mark- edly favorable present status of quality assurance, but they have problems, such as the examination sample (matrix and spike materials in abnormal specimens) and valuation basis. Improved proposals for EQSP have been developed: EQSP with fresh blood, combination of open with blind surveys, and control Serum using donated blood (MacRM). [Review].

(Objective) We examined the morphology and function of lower urinary tract in order to know characteristics of stress urinary incontinence after pelvic organ prolapse (POP) surgery. (Methods) One hundred twenty-five female patients (mean age 64.9 years, mean parity 2.2, mean body mass index (BMI) 24.4) were performed anti-incontinence surgery for stress urinary incontinence. Sixty-one of 125 patients underwent POP surgery before anti-incontinence surgery. They were divided into groups as follows: post-POP surgery group and non-POP surgery group. All patients underwent one-hour pad test, chain cystourethrography (chain CG), Urodynamic studies (UDS) as preoperative assessment. Midurethral sling procedure was performed as an anti-incontinence surgery. Preoperative assessment criteria and postoperative treatment results were compared between two groups. (Results) Post-POP surgery group showed a significantly greater amount of urinary leakage per 1-hour pad test than non-POP surgery group (65.2±74.3 g vs 14.3±25.2 g, p<0.05). The diagnosis of type III urinary stress incontinence (Blaivas' classification) was more frequently diagnosed in post-POP surgery group than non-POP surgery group (50.0% vs 25.0%, p<0.05). Maximum urethral closure pressure (MUCP) and functional profile length (FPL) of post-POP surgery group were lower than those of non-POP surgery group (27.4±9.2 vs 35.7±14.7, p<0.05, 27.3±4.7 vs 29.9±5.0, p<0.05). Postoperative treatment results of post-POP surgery group were worse than those of non-POP surgery group (78.7% vs 92.2%, p<0.05). (Conclusions) Post-POP surgery group showed more severe urinary incontinence, lower urinary function and lower cure rate. Therefore we should keep in mind when approaching urinary stress incontinence.

Here, we report three cases of moyamoya disease with a history of Kawasaki disease. A 33-year-old man was found to have stenotic lesions of the internal carotid arteries(ICAs)on both sides at a nearby hospital where he visited complaining of headache and lisping. He had received immunoglobulin therapy for Kawasaki disease at the ages of 1, 2, and 6 years. MRI showed only a chronic ischemic lesion in the white matter. Angiography showed occlusion at the terminal portion of the ICAs on both sides. He was diagnosed with moyamoya disease, but as he had no symptoms and preserved cerebral blood flow (CBF), he was kept under observation. An 8-year-old boy was diagnosed with moyamoya disease and underwent right encephaloduroarteriosynangiosis at a nearby hospital. He had received immunoglobulin therapy for Kawasaki disease at the age of 1 year. His ischemic symptoms worsened. Although MRI detected no apparent ischemic lesion, angiography revealed severe stenosis at the terminal portions of the ICAs on both sides, and 123I-IMP SPECT showed CBF impairment. Bilateral direct bypass was performed. His father was subsequently also diagnosed with moyamoya disease. A 4-year-old girl with epilepsy was diagnosed with moyamoya disease at a nearby hospital. She had been treated with aspirin for Kawasaki disease at the age of 1 year. MRI detected no remarkable ischemic lesions, but angiography revealed mild stenosis at the terminal portions of the ICAs on both sides. Five months later, her ischemic symptoms were worsening with progressing stenotic lesions, and she underwent bilateral direct bypass.

The standardization of clinical laboratory and compatible clinical data is needed for accurate diagnosis in routine medical practice or medical care. An external quality survey program (EQSP) in clinical laboratory testing and recommendation methods for laboratory test and/or standard materials are proposed. Many megaEQSPs in Japan have problems, such as examination samples (matrix and spike materials in abnormal specimens) and valuation basis. Proposals for EQSP are being developed: EQSP with fresh blood, EQSP using internal quality control, and control serum using donated blood (MaCRM).

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.

MicroRNA in body fluid is called circulating microRNA and is expected to be a non-invasive stable biomarker of various diseases. In real-time RT-PCR of circulating microRNA, synthetic non-human microRNA, such as cel-miR-39, is used as spike-in control RNA instead of endogenous control RNA. Spike-in control RNA, which is added into sera or plasma just before RNA extraction, does not reflect microRNA degradation in the period between blood sampling and RNA extraction. Therefore, it is essential to prevent degradation of circulating microRNA in this period for better reproducibility of the quantification of microRNA using spike-in control. To address this issue, we analyzed the stability of cel-miR-39 on ice and circulating miR-21 and miR-223 in whole blood and serum. The synthetic cel-miR-39 in RNase-free water was stable for at least 3 hours on ice. Degradation of miR-21 and miR-223 in whole blood was not observed for 3 hours at room temperature. However, miR-223 in serum was apparently degraded within 24 hours at 4°C and the stability levels of miR-21 and miR-223 in serum were significantly different (fold changes of miR-21 and miR- 223 within 24 hours were 0.891 and 0.485, respectively). These results show that it is essential to avoid long-term storage of sera at 4°C to prevent degradation of microRNA in the quantification of circulating microRNA using spike-in control.

We assessed the outcomes of high-risk prostate cancer patients who received radical prostatectomy (RP), external beamradiation therapy (EBRT) or androgen deprivation therapy (ADT). Two hundred nineteen patients who were diagnosed with pathologically confirmed high-risk prostate cancer as defined by D'Amico between 2005 and 2011 were included in this study. Of them, 74 patients underwent RP. The 5-year cancer-specific survival (5yCSS) and 5-year PSA recurrence-free survival (5yPRFS) rates were 100 and 67.2%, respectively. A positive surgical margin and Gleason score≧8 were risk factors for PSA recurrence. The 5yPRFSs were 100, 74.4% and 'unmeasurable' for patients with 0, 1 and 2 risk factors, respectively. Ninety patients underwent EBRT. The 5yCSS and 5yPRFS rates were 95.2 and 74.2%, respectively. Fifty-five patients underwent ADT alone. Their 5yCSS and 5yPRFS rates were 93. 3 and 64. 3%, respectively. There was no significant difference in 5yCSS and 5yPRFS rates among the treatment groups. These results show that RP can be a treatment option for high-risk prostate cancer patients.

Objective: We studied the association between uterine myoma and recurrent pelvic organ prolapse (POP) after transvaginal mesh (TVM) repair., Methods: Between June 2010 and January 2012, 103 female patients (mean age 67.8 years, mean parity 2.3, mean body mass index (BMI) 23.7) with POP underwent TVM procedures at our hospital. Sixtynine patients were qualified as stage 3 according to the POP quantification (POP-Q) system and 34 patients were stage 4. Twenty-six patients underwent anterior TVM (A-TVM) and 77 patients underwent anterior and posterior TVM (AP-TVM). All patients underwent a physical examination using the POP-Q system before and 6 month after surgery. Recurrence of prolapse was defined according to the International Continence Society by a measured value ≥ - 1, as most dependent portion of POP stage 2 or greater. One hundred-three patients were divided into group with uterine myoma larger than 5 cm in diameter and group without uterine myoma. Anatomical outcomes before and after TVM repair were compared between two groups., Results: Preoperative Aa value, Ba value and gh value in group with uterine myoma were greater than in group without uterine myoma. Postoperative Aa value and Ba value in group with uterine myoma were greater than in group without uterine myoma, too. Postoperative recurrence of prolapse of stage 2 or greater was not found a statistical difference between two groups., Conclusions: The risks of anterior vaginal wall descent seem to be high in POP with uterine myoma. Therefore it should be kept in mind on treatment choice.

Mixed pial-dural arteriovenous malformation(AVM) is currently defined as a malformation fed by both the pial and meningeal arteries. Although many cases of mixed pial-dural AVM have been reported, few papers have addressed its pathological locations. The authors report a case of a 43-year-old male patient with mixed pial-dural AVM in the occipital lobe, consisting of two distinct nidi located on the tentorium and in the cerebral parenchyma respectively. The lesions were surgically resected, and the pathological examination confirmed that both were indeed AVM. The authors discuss this rare type of AVM, focusing on the possible pathogenic mechanism thereof.

Pathogenesis of venous thromboembolism (VTE) known to be complex and multifactorial process involves the interaction of acquired factors and genetic predisposing conditions. Deficiency of natural anticoagulant factors such as antithrombin (AT), protein C and protein S increases the risk of a VTE. Recently, we have reported novel mechanism of hereditary thrombosis in a Japanese family, in which AT resistance was associated with a missense mutation (p.Arg596Leu) in the prothrombin gene named prothrombin Yukuhashi. The mutant thrombin showed a low clotting activity, but a severely impaired inactivation by AT, resulting in a susceptibility to thrombosis. We have developed a new laboratory test to evaluate AT resistance in plasma. Prothrombin mutation causing AT resistance has found in Caucasian, not only in Japanese.

Here, I examined the efficacy of neoadjuvant chemotherapy( NAC) with S-1/CDDP( SP) in my hospital. The subjects were 8 patients with advanced gastric cancer who had undergone NAC since 2007 (7 men and 1 woman; median age, 70 years). The staging before the treatment was Stage II A: 1 patient, II B: 2 patients, III B: 3 patients, III C: 1 patient, and IV: 1 patient. The macroscopic type of 3 and 5 patients was large type 3 and type 4, respectively. Gastrectomy was performed following the NAC with SP. The NAC response rate was 62.5%. In the histological response criteria, 1 patient was grade 0, 2 patients were grade 1a, 2 patients were grade 1b, and 3 patients were grade 2. Adverse events following the NAC were in the acceptable range. We noted that the presence of Stage IV or grade 0 histological response criteria to NAC indicated poor prognosis. Thus, I believe that preoperative surgery after NAC in Stage III gastric cancer should be considered to be curative.

A 61-year-old man was referred to our hospital with the chief complaint of right leg weakness. Abdominal magnetic resonance imaging (MRI) and computed tomography (CT) demonstrated a ureteral tumor and a neighboring massive retroperitoneal tumor in addition to retroperitoneal lymph node and right renal metastases. The tumor was diagnosed as upper tract urothelial carcinoma (cT4N1M1) by percutaneous tumor biopsy. As the patient achieved a partial response after three courses of combination chemotherapy with gemcitabine and cisplatin, he received total nephroureterectomy and lymph node dissection. The pathology showed no viable cancer cells, demonstrating a pathological complete response. He remains alive after 26 months with no evidence of disease.

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

A 76-year-old man underwent right hemihepatectomy and partial hepatectomy of segment II for hepatocellular carcinoma (HCC) at our institution. Four months after the primary hepatectomy, the patient complained of severe back pain on the right side, and computed tomography and bone scintigraphy indicated metastasis of the eighth rib on the right side. Because no metastatic lesions were observed in any organ, the patient underwent surgical intervention for the rib metastasis in December 2011. Histopathological findings confirmed that the metastatic tumor originated from the HCC and that cancer tissues were absent from the surgical margins. Postoperative radiotherapy was additionally performed for preventing local recurrence. The sharp cancerous pain disappeared completely, and the patient was lived without recurrence 6 months after the second surgery. In cases where intrahepatic or other metastatic lesions are controllable and only a solitary bone metastatic lesion is evident, surgical resection is effective in HCC patients with bone metastasis.

We report here on a case of a 27-year-old woman in her first pregnancy. She was diagnosed with idiopathic thrombocytopenic purpura (ITP) at the age of 14 years. At 36 weeks of gestation, she was admitted to our hospital due to thrombocytopenia. We initially suspected ITP exacerbated by pregnancy. Laboratory results revealed mild anemia, thrombocytopenia (5.0×10(9)/l), and slightly elevated liver enzymes and lactate dehydrogenase. The next day, hemoglobin fell to 6.6 g/dl. Thrombotic thrombocytopenic purpura (TTP) was suspected on the basis of hemolytic anemia with schistocytes and a negative Coombs' test. Plasma exchange and methylprednisolone were initiated immediately. ADAMTS13 analysis showed a severe deficiency in ADAMTS13 activity but no inhibitors. At Day 6, the platelet count rose to 223×10(9)/l and she delivered a live baby by cesarean section. Currently, the patient receives fresh frozen plasma infusions every 2 weeks due to suspected Upshaw-Schulman syndrome.

Recently, transparency of the organization administration and patient-centered medical care such as patient service and satisfaction have been demanded in the medical field. The role of the clinical laboratory, one of the organizations in the medical field, is to provide quality laboratory data to improve diagnosis and treatment. Other than clinical laboratory facilities, education and the ability of staff to use it, the management of the organization must be appropriate to produce high quality laboratory data. International guidance on how to manage a laboratory is shown in ISO 15189. Clinical laboratories with ISO accreditation in Europe, Australia and Asia are increasing. On the other hand, only 60 institutions (10 national university hospitals, 4 public private university hospitals, 12 private hospitals and 34 referral laboratories) are accredited in Japan. Six speakers spoke at this symposium about the accreditation system of ISO 15189, the experiences of the acquiring institution and the effect of acquisition, as well as the future prospects of ISO 15189. This was a good opportunity to become informed about the current situation of ISO 15189 in Japan and internationally.

Purpose: Anastomotic stricture (AS) following radical prostatectomy (RP) decreases patients' quality of life. It occurs in 0.5% to 32% of men after open radical retropubic prostatectomy (RRP), although its etiology is poorly understood. In a series of patients who received RRP, we analyzed the incidence, possible predisposing factors, and management of AS after RP., Materials & Methods: Between April 1997 and March 2006, 129 consecutive patients underwent RRP in our hospital. Anastomosis between the bladder neck and urethra was performed with interrupted anastomosis using four 2-0 absorbable sutures. AS was diagnosed when a 16Fr. panendoscope could not be passed. We assessed the relationship between the management method for AS and time interval between the surgical procedure and diagnosis of the stricture. The relationships between comorbidities identified preoperatively (hypertension [HT], diabetes mellitus [DM], cardiovascular disease [CVD], cerebral infarction [CI] and smoking history) and the incidence of AS were determined. Risk factors, including age, body mass index [BMI], preoperative PSA, total prostate volume, operative time, blood loss, Foley duration, amount of stress urinary incontinence (SUI) per day, amount of drain output, pathological T stage, Gleason sum and surgical margin status were also assessed., Results: The rate of AS after RRP was 10.9% (14/129). In 10 patients (72%), AS occurred within 3 months of surgery, in 2 (14%) it occurred at 4-12 months after surgery and in 2 (14%) more than 12 months after surgery. In univariate and multivariate analyses, intraoperative bleeding of 1,800 ml or more was independently the strongest predictor of AS. In two patients a urethral bougie was used and 11 underwent internal urethrotomy. Only 1 patient underwent transurethral resection. Of the 8 patients whose strictures were diagnosed within 3 months after surgery and underwent internal urethrotomy, 6 had recurrent anastomotic strictures., Conclusions: Risk factors for AS are thought to be multifactorial. Intraoperative blood loss was significantly associated with the development of anastomotic stricture. We should understand that anastomotic stricture following radical retropubic prostatectomy is not a rare morbidity and should inform patients about the possibility of postoperative AS.

Objectives: Mainstream smoke from cigarettes contains tobacco-specific N'-nitrosamines (TSNAs) listed as Group 1 and 3 carcinogens by the International Agency for Research on Cancer (IARC). Herein, we report on a method of measuring the concentrations of TSNAs in mainstream smoke from the ten top-selling Japanese cigarette brands using an ISO regime by International Organization for Standardization (ISO) and HCI regime of Health Canada., Methods: Tar in mainstream smoke was collected on a Cambridge filter pad using a smoking machine. The filter pad was immersed in 40 mL of ammonium acetate (pH 6.8) and shaken for 30 min. The extract was then loaded into a C18 column. After washing with 5 mL of 10% methanol and eluting with 5 mL of 70% methanol, the eluate was concentrated to 1 mL for LC-MS/MS analysis., Results: The concentrations of TSNAs in all cigarette brands were higher when determined using the HCI regime than when determined using the ISO regime. Furthermore, the concentrations of TSNAs measured using both the ISO and HCI regimes showed negligible correlation to the tar and nicotine concentrations indicated on package labels. The cigarette samples used in the study were categorized into four classes: ultralow-, low-, medium-, and high-yield brands, which corresponded to 1, 3-6, 8-10, and 14 mg tar/cigarette, respectively. The concentration of TSNAs in ultralow-yield cigarettes was 210 ng/cigarette, as measured using the HCI regime, which was nearly equal to that in high-yield cigarettes (180 ng/cigarette)., Conclusions: Exposure to TSNAs from mainstream smoke from ultralow-yield cigarettes is comparable to that from high-yield cigarettes. To properly evaluate the risk of smoking, not only the concentrations of tar and nicotine but also those of other chemicals, including TSNAs, should be printed on package labels.

A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.

Objectives: There are several recommendations on the prevention of hypothermia during snow shoveling. However, there seemed to be insufficient evidence supporting these recommendations because they are not based on data from actual snow shoveling research. The purpose of this study was to investigate changes in brain temperature (tympanic temperature) and visceral temperature (rectal temperature) during snow shoveling among healthy young males., Methods: Eight healthy young males (age, 23.6 ± 2.4 years; weight, 69.7 ± 6.1 kg; height, 172.8 ± 7.3 cm) performed snow shoveling with an ordinary-size shovel for 15 min at their own pace in a rural snowfall area in December, 2009. Rectal temperature (Tre) and tympanic temperature (Tty) were measured 5 times (at rest, 5th (Ex5), 10th (Ex10), and 15th (Ex15) minute of snow shoveling; and 5th (Rec5) minute of recovery phase). The room temperature was 18.6 ± 0.7°C and the atmospheric temperature was 3.8 ± 2.6°C., Results: Tre continued to increase from at rest to Ex15. Tre at Ex15 (37.7 ± 0.3°C) was significantly higher (p < 0.05) than that at rest (37.2 ± 0.3°C). Tty at rest (36.7 ± 0.2°C) and Tty at Ex5 (36.6 ± 0.3°C) decreased significantly (p < 0.05) at Ex10 (36.2 ± 0.6°C). A significant negative correlation between changes in Tre and Tty were observed during snow shoveling (r = -0.49, p < 0.05)., Conclusion: Discrepancy between changes in brain temperature (tympanic temperature) and visceral temperature (rectal temperature) should be taken into consideration in the prevention of disease development during snow shoveling in a cold environment.

Unlabelled: An asymptomatic 77-year-old woman was referred in 2000 because multiple nodular shadows were found on chest X-ray films on a medical checkup. Chest computed tomography (CT) showed bilateral multiple ground-glass opacities and ill-defined nodules. A transbronchial lung biopsy was performed via bronchoscopy, but the specimens did not yield any specific findings. She was then monitored without therapy as an outpatient. In November 2005, chest CT imaging showed that the size and density of the ground-glass opacities and nodules had increased. In January, 2006 video-assisted thoracic surgery (VATS) was performed to obtain a definitive diagnosis. Based on histological and immunohistochemical examinations, primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was diagnosed. She has been followed up without any additional treatment since., Conclusion: Multiple ground glass opacities and nodules are rare chest CT findings in pulmonary MALT lymphoma.

We experienced a case with a falsely low value by a blood MMP-3 measuring reagent employing a recently structured new latex immunoturbidity. The case involved duplicate orders for one patient in a single day, and the blood collection amounts and measured values were approximately 6.0 mL and 206.6 ng/mL and approximately 1.0 mL and 107.5 ng/mL. The latter MMP-3 concentration was 48% of the former, showing a low tendency. Therefore, an experiment was conducted by adding serum to the blood collection tubes with or without a serum-separating agent of four different manufacturers (Terumo, Sekisui Medical, Nipro, and Becton Dickinson), and similar results as our experienced case were obtained with the Terumo tube with serum-separating agent, which had been used in this case. The amount of whole blood was obtained by conversion assuming a hematocrit value of 40%, and the addition ratio was calculated relative to the predetermined amount of the tube showing a falsely low value. Falsely low values were observed at < or = 56%, < or = 21%, < or = 20%, and , or = 33% for Terumo, Sekisui Medical, Nipro, and Becton Dickinson, with tubes containing a serum-separating agent, and at < or =10%, < or =8%, < or =19%, and < or =14% for Terumo, Sekisui Medical, Nipro, and Becton Dickinson, respectively, with plain tubes. Falsely low values were not observed with the 10-ml plain tube of Terumo and the 9-ml plain tube of Nipro (untreated tube). Based on these results, care should be taken if samples are below the predetermined amount of the blood collection tube to determine the serum MMP-3 by this method.

We report a case of myeloid sarcoma in the anterior mediastinum. The patient was a 33-year-old man with a chief complaint of right shoulder pain, right upper limb edema, and cough. Chest contrast-enhanced computed tomography (CT) revealed a partially enhanced anterior mediastinal tumor. A CT-guided biopsy was then performed, and a Hematoxylin-eosin (HE) stain revealed mitosis of tumor cells and other cells, including eosinophils. Immunohistochemical stains with myeloperoxidase, CD34, CD43, CD68 and c-Kit tests were positive for tumor cells. Due to a pathological diagnosis of myeloid sarcoma, he was treated with chemotherapy based on a diagnosis of acute myelogenous leukemia. After complete remission was obtained, the patient visited another hospital to receive an unrelated bone marrow transplantation. Although it rarely occurs as a mediastinal tumor, the prognosis of myeloid sarcoma is unfavorable, and thus should be taken into consideration as a differential diagnosis.