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A 42-year-old women was refer with a left breast tumor. Mammography reveals category 4 tumor and breast sonography showed a tumor on her upper lateral portion with axillary and intra-thoracic mammary lymph node metastases. We treated by KEYNOTE-522 regimen that may proofed best effective for triple negative breast cancer(TNBC). Because of past history treating acute lymphatic leukemia, which had to regulate the amount of doxorubicin. But in this case acquired pCR with no adverse effects. In this report we experienced a case of TNBC with a history of leukemia treated by immune check point inhibitor. Even though, a case with regulated use of chemotherapy, immune checkpoint inhibitor revealed effective for a high risk TNBC.

A 71-year-old woman was referred to our hospital for a right breast mass urgency. A CT scan revealed a large right breast tumor with skin involvement. Biopsy results confirmed the diagnosis of Luminal-HER2 type invasive ductal carcinoma. Chemotherapy was initiated with a regimen of paclitaxel, trastuzumab, and pertuzumab. Initially, the tumor flattened and significantly decreased in size. However, after 9 months of treatment, disease progression occurred, leading to sequential changes in the treatment regimen to T-DM1 and T-DXd. Despite these efforts, the tumor continued to grow rapidly. At 13 months after starting chemotherapy, the treatment effect was unsatisfactory, prompting a decision to perform a total mastectomy, including resection of the right breast tumor and the pectoralis major muscle, followed by skin grafting. The histopathological effect of the treatment was judged as Grade 1b, with intermediate tumor margins. Postoperatively, the patient received radiation therapy to the chest wall, followed by continued treatment with trastuzumab and pertuzumab. As of 2 years after surgery, no recurrence has been observed.

Case 1: A 49-year-old woman underwent NAC followed by surgery for left breast cancer. Two years later, she experienced recurrence with lymph node and liver metastases. Nine months after, multiple brain metastases appeared, which shrank after whole-brain radiation therapy. One year post-radiation, the tumors regrew, and T-DXd was administered, leading to a positive response. However, 22 months later, the disease progressed, and she died from carcinomatous meningitis 26.6 months after treatment. Case 2: A 48-year-old woman had NAC followed by surgery for right breast cancer. One year and 9 months post-surgery, she had a brain metastasis recurrence, treated with resection and Gamma Knife. Six months later, the tumors regrew and were resected again. One year after, multiple brain metastases appeared, treated with whole-brain radiation therapy. Initially, the tumors shrank but regrew, so T-DXd was administered, achieving a complete response. However, 19.1 months later, the disease progressed with lung metastases, and she died from carcinomatous meningitis 21.9 months post-treatment. Case 3: A 47-year-old woman with Stage Ⅳ left breast cancer(lung, liver, and bone metastases)continued chemotherapy. After multiple brain metastases appeared, whole-brain radiation therapy and T-DM1 led to tumor shrinkage. However, the tumors rapidly regrew, and T-DXd was started, resulting in a positive response. Ten months later, the disease progressed, and she died from carcinomatous meningitis 17.7 months after initial treatment.

Delayed cerebral ischemia(DCI) is one of the most significant complications of subarachnoid hemorrhage. Despite significant evolution in understanding DCI pathophysiology, vasospasm affecting cerebral vessels of large and moderate diameters remain the only clinically measurable component of DCI and is therefore the primary target for intervention in the postoperative management of subarachnoid hemorrhage. In Japan, fasudil hydrochloride and ozagrel sodium are widely used to prevent vasospasms; however, their effects are sometimes insufficient. Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage. This was demonstrated in a recent randomized phase 3 trial, leading to the approval of clazosentan by the Pharmaceuticals and Medical Devices Agency in Japan. Recent advances in our understanding of subarachnoid hemorrhage will facilitate improved management to reduce the incidence of DCI.

The patient was a 51-year-old woman at the time of diagnosis of left breast cancer. She underwent a mastectomy and axillary dissection. Pathological findings were invasive ductal carcinoma of the breast, tumor diameter 25 mm, and metastasis in 2 of 16 removed axillary lymph nodes. The subtype was triple negative. Postoperative chemotherapy was administered, and the patient was followed by follow-up imaging. At the age of 63 years, ultrasonography showed local recurrence, and local mass excision was performed. Genetic abnormalities were suspected since she had a family history of breast cancer, and it was a recurrent case. After genetic counseling, she underwent genetic testing, which revealed a BRCA1 pathogenic variant, so we initiated imaging surveillance. At age 65, a chest CT scan was performed due to respiratory symptoms, and she was diagnosed with multiple lung metastases. Respiratory symptoms improved at the examination 1 month after administration of Poly ADP ribose polymerase(PARP)inhibitor, and the metastatic masses shrank at the CT scan 3 months later. She continues to maintain CR and has no respiratory symptoms at present.

A 79-year-old man was detected with anemia on medical examination and underwent gastroscopy at the previous hospital. Gastroscopy revealed a 15-mm ulcerative lesion(Type 0-Ⅱc plus Ⅲ)on the greater curvature of the upper gastric body. Tumor biopsy showed well-differentiated adenocarcinoma. The patient was suspected of deep submucosal invasion due to poor stretching of the gastric wall and the ulcer depth; hence, he was transferred to our hospital for surgery. When gastroscopy was repeated, the ulcer was found to be scarred(Type 0-Ⅱc), thereby indicating the occurrence of intramucosal carcinoma; hence, endoscopic submucosal dissection was performed. The pathological finding showed 10×6 mm, tub1, pT1a, ly0, v0, pUL1, pHM0, pVM0, suggesting a curative resection. Early gastric cancer of the depressed type is known to develop a malignant cycle with repeated improvements and exacerbations of the ulcer. Diagnosing the depth of tumor invasion is particularly difficult when there is an active ulcer. For small lesions with active ulcers, repeating gastroscopy might allow for correct diagnosis and appropriate treatment.

Most patients with non-hemorrhagic and non-ischemic vertebral artery dissections(VADs)are likely to recover with good outcomes. In contrast, some cases of uneventful outcomes have also been reported. Therefore, whether surgical treatment or prolonged follow-up should be utilized for each case remains controversial. In this study, we retrospectively investigated the radiological features and changes in non-hemorrhagic and non-ischemic VADs during the follow-up period. We reviewed the medical records of 15 consecutive patients with VADs without hemorrhage or ischemic lesions diagnosed between 2008 and 2017; all patients reported severe occipital headache. All hemorrhagic and ischemic lesions were categorized into morphological types according to the initial radiological findings. The following morphological types of dissections were observed: six cases, pearl and string type; six cases, dilatation type; two cases, stenosis type; and one case, occlusion type. We observed morphological aggravation in four cases, and among them, three underwent surgical interventions. Seven patients recovered during the follow-up period, and five of them showed marked radiological changes within 2 months. One patient died fromethe clinical onset. Therefore, careful follow-up radiological imaging is presumably necessary for patients with non-hemorrhagic and non-ischemic VADs, within at least 2 months of the clinical onset because of the tendency of VADs for rapid morphological changes during that period.

Recently, the interest in cancer genomic medicine has increased, owing to the powerful and cost-effective technology of next-generation sequencing(NGS), which allows rapid identification of a large number of gene mutations. TP53 mutations are frequently found in solid cancers, especially in esophageal squamous cell carcinoma(ESCC), wherein the frequency of TP53 mutation is considered to be 90% or more. However, there is no clinical targeted therapy as yet utilizing TP53. Here, we aimed to characterize TP53 mutations associated with ESCC, in order to assess its feasibility as a therapeutic target. We extracted DNA and RNA from specimens of ESCC patients and analyzed them using NGS, which revealed different TP53 mutations. Based on previous reports, it is considered that different TP53 mutations lead to different functions of the protein, and subsequently account for varied prognosis in squamous cell carcinoma of the head and neck. We also performed cell viability assay using ESCC cell lines with different TP53 mutations and 2 kinds of p53-targeted drug and found differences in the growth inhibition of the cell lines. Although individual treatment can be determined depending on the type of TP53 mutation, it would be necessary to further examine the interaction of TP53 with other genes to determine its therapeutic efficacy as a target.

Immunocheckpoint inhibitors including anti-PD-1 antibody have shown certain therapeutic effects on various cancer types. They have also attracted great attention as novel cancer treatment options in addition to surgical resection, chemotherapy, and radiation therapy. Herein, we report a case of gastric cancer that was successfully treated with conversion surgery after nivolumab treatment. The patient was 68 years old and male. Upper gastrointestinal endoscopy revealed a type 3 tumor in the antrum, and he was referred to our department for further examination. The gastric cancer was diagnosed as cT4aN2M0, cStage ⅢA, and he was administered SOX as the first-line and nab-PTX/RAM as the second-line treatment, which was also a PD. As the third-line treatment, nivolumab showed remarkable reduction of the tumor after initiation, and after 14 courses, conversion surgery was performed. The patient remains alive without recurrence.

The susceptibility of 1578 Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015 was tested to penicillin G (PCG), cefotaxime (CTX), ceftriaxone (CTRX), cefditoren (CDTR), meropenem (MEPM), erythromycin (EM) and levofloxacin (LVFX). Although no significant differences were observed, the percentage of strains with a minimal inhibitory concentration (MIC) of PCG of <0.1pg/mL increased from 55.5% (2011) to 64.0% (2015), whereas that of strains with MIC of ≥2μg/mL decreased from 14.8% to 9.5%. From 2011 to 2015, the percentage of strains with MIC ≤0.12ug/mL increased from 18.9% to 28.9% for CTX, from 20.5% to 30.2% for CTRX, from 29.2% to 40.9% for CDTR, and from 69.6% to 80.6% for MEPM. EM-resistant strains with MIC ≥22μg/mL accounted for as much as approximately 90% each year. One LVFX-resistant strain with MIC 8pg/mL has been detected each year since 2013.

A 4mg/kg dose of tebipenem pivoxil (TBPM-PI) was administered twice daily for 3 days to 34 pediatric patients with pneumonia who had chest X-ray findings indicative of pneumonia and CRP values of at least 3.0 mg/dL. The clinical effects of this regimen were evaluated by retrospectively examining medical charts for the period from April 2012 to March 2015. The patients were 6 months to 8 years old, with serum CRP values ranging from 3.06 to 14.25 mg/dL. Fever resolved within 24 hours and respiratory symptoms improved within 3 to 5 days after the start of treatment in all 34 patients. Although CRP was positive in 28 of 30 patients at the end of the treatment period, none of these children showed worsening of pneumonia. Eight patients (23.5%) experienced adverse drug reactions including diarrhea. These results indicate that a 3-day course of TBPM-PI is useful for treating pediatric pneumonia.

Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.

We report the case of a 48-year-old female patient with HER2-positive and hormone receptor-negative breast cancer with multiple liver metastases. She underwent 6 cycles of FEC followed by docetaxel plus trastuzumab (TZB), resulting in a clinical complete response. After 15 cycles of a TZB-containing regimen, she complained of dizziness and nausea, and imaging examinations revealed multiple brain metastases. Whole-brain irradiation(33.6 Gy) was performed, and the chemotherapy regimen was changed to lapatinib (LAP: orally at 1,250 mg/day, every day) and capecitabine (CAP: orally at 2,000 mg/m2, every day for 2 weeks, followed by a 1-week rest interval, as 1 cycle). After 6 weeks of the new treatment, magnetic resonance imaging revealed marked shrinkage of brain metastases. A clinical complete response was maintained for 19 months. While brain metastasis is an important problem with treatment with TZB, LAP is drawing attention because of its ability to pass the blood-brain barrier because of its small molecular weight. LAP/CAP combination therapy may be an effective treatment option for brain metastases of HER2-positive breast cancer in which TZB essentially has no effect.

We report a case of atherothrombotic embolization that developed with slowly progressive symptoms and required differential diagnosis from metastatic tumor recurrence. A 64-year-old man with a history of lung cancer and metastatic brain tumor was carefully followed at our outpatient department for tumor recurrence. Five years after surgery for brain metastasis and whole brain radiation therapy, he had no recurrence and systemic disease was well controlled. At a routine follow up in October 2013, he complained of slight right arm dysesthesia. Follow up brain magnetic resonance (MR) imaging revealed no lesion. Two months later, he developed right hemiparesthesia and gait disturbance. Spinal MR imaging was unremarkable. However, at a routine follow up in January 2014, multiple enhancements were detected near the resection cavity and regions delineating the sulci. At first, this was diagnosed as tumor recurrence. However, 3 days later, additional MR imaging detected new multiple small infarctions after worsening right hemiparesis and dysarthria. With the diagnosis of embolic stroke, we searched for an embolic source. Cardiogenic embolization and carotid bifurcation stenosis studies were negative, but severe stenosis and thrombosis were detected near the left common carotid artery origin. This site was in the field of radiation the patient received as treatment for primary lung cancer.

Moyamoya disease is characterized by idiopathic steno-occlusion at the terminal portion of the internal carotid artery with concomitant abnormal vascular networks that can lead to transient ischemic attacks and hemorrhagic stroke with symptoms of headache, confusion, dizziness, ataxia, seizure, and cognitive and personality changes. Because these symptoms also occur in patients with type 1 diabetes mellitus(T1DM), patients with both diseases might go unnoticed and without the less common diagnosis of akin moyamoya disease, accurate diagnosis and treatment could be delayed. Here, we report the case of a 32-year-old woman with past history of T1DM for 26 years presenting with right amaurosis, which was diagnosed as akin moyamoya disease even though she had suffered right incomplete hemiparesis 2 years ago. She underwent superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in the left hemisphere without complication. She had no cerebrovascular events postoperatively. Although akin moyamoya disease associated with T1DM is rare in Japan, we recommend that clinicians consider the coexistence of both diseases when evaluating patients with T1DM who have neurologic signs or symptoms and not overlook the possibility of cerebrovascular diseases, such as akin moyamoya disease.

A 42-year-old man with a history of hypertension and obesity presented with transient dysesthesia in his left upper and lower extremities and was found to have moyamoya syndrome associated with atherosclerosis. He underwent superficial temporal artery-middle cerebral artery anastomosis with pial synangiosis in the right hemisphere 1 month after the onset of symptoms. Prophylactic blood pressure lowering(<130 mmHg)as well as minocycline administration was introduced immediately after surgery to prevent symptomatic cerebral hyperperfusion, but he developed pulmonary edema due to congestive heart failure several hours after surgery. We subsequently allowed his systolic blood pressure to be under 140 mmHg, which dramatically improved his cardiopulmonary condition. The neurologic status of the patient was unremarkable, but (123)I-IMP-SPECT the day after surgery demonstrated an intense increase in the cerebral blood flow at the site of the anastomosis. Moreover, postoperative magnetic resonance angiography demonstrated the bypass as thick, high signal. Together, these results led us to the diagnosis of cerebral hyperperfusion. The patient did not demonstrate any neurological sign during the entire perioperative period, but CT scan performed 7 days after surgery revealed a delayed intra-cerebral hemorrhage in the right temporal lobe due to the cerebral hyperperfusion. We continued to mildly lower his blood pressure, and neither ischemic nor hemorrhagic events were subsequently observed; he was discharged without neurological deficit 2 weeks after surgery. In conclusion, congestive heart failure and pulmonary edema are potential complications of the perioperative management of moyamoya syndrome with atherosclerotic background. Moreover, cardiopulmonary complications should be mentioned as a potential pitfall of the intensive perioperative management of moyamoya disease to counteract with cerebral hyperperfusion.

Incarcerated diaphragmatic hernia after laparoscopic right hepatectomy is very rare. An 81-year-old man underwent laparoscopic right hepatectomy for giant hepatic hemangioma. Twenty months after the surgery, he began to complain of nausea and abdominal pain and was brought to our hospital. Chest X-ray showed an abdominal gas shadow above the right diaphragm and computed tomography showed herniation of the colon into the right thoracic cavity. We diagnosed ileus due to incarcerated diaphragmatic hernia and performed emergency operation under laparoscopic surgery. After successfully reducing the prolapsed colon back to the abdominal cavity, the diaphragmatic hernia orifice was repaired. Incarcerated diaphragmatic hernia sometimes causes the fatal state. Clinicians must therefore consider such findings a late complication of laparoscopic hepatectomy.

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of commonly used clinical antimicrobial drugs were examined for 76 strains of Streptococcus pneumoniae isolated between 2006 and 2011 from pediatric patients with invasive pneumococcal infection. Patients from whom bacterial strains were isolated ranged from 4 months to 6 years old and included 50 infants (65.8%) 1 year old and 10 (13.2%) less than 1 year old, i.e., 79.1% of all patients studied. In diagnosis, 38 (50.0%) had occult bacteremia, 34 (44.7%) pneumonia, 3 (3.9%) meningitis, and 1 (1.3%) sepsis. Infections in all but one case who died of sepsis were treated without sequelae. The most frequent capsular serotype among isolates was 6B (20 strains, 26.3%), followed by 19 F (13 strains, 17.1%) and 14 (9 strains, 11.8%). Serotypes for 55 strains (72.4%) corresponded to those contained in heptavalent pneumococcal conjugate vaccine. In classification by resistance based on mutations in penicillin-binding protein genes, 32 were penicillin-resistant S. pneumoniae (42.1%), 35 penicillin intermediate-resistant S. pneumoniae (46.1%), and 11 penicillin-susceptible S. pneumoniae (11.8%). MIC90/MBC90 of drugs were as follows: ampicillin 4/4 microg/mL, cefotaxime 0.5/0.5 microg/mL, ceftriaxone 1/2 microg/ mL, panipenem 0.125/0.125 microg/mL, meropenem 0.5/0.5 microg/mL, and doripenem 0.25/0.25 microg/mL.

Infantile dural arteriovenous fistula is a rare cerebrovascular malformation carrying a poor prognosis with an anatomic cure of only 9%. Endovascular embolization is mainly selected to treat this entity, aiming to obtain normal development of the patients. We present a case of a 20-month-old girl with epilepsy. Digital subtraction angiography revealed a dural arteriovenous fistula involving the right transverse sinus. The arteriovenous fistula was fed by multiple dural branches from the middle meningeal, occipital, meningohypophyseal, and anteroinferior cerebellar arteries. The right transverse sinus was transvenously embolized with platinum coils. Although the shunt flow remained, the patient was liberated from epilepsy. Nine months later, the patient suffered from a recurrence of epilepsy. Digital subtraction angiography demonstrated some increase in shunt flow. Right middle meningeal, occipital, posterior deep temporal, and tentorial arteries were transarterially embolized using N-butyl cyanoacrylate, followed by complete surgical resection of the right transverse sinus. The shunt flow disappeared after surgery, and her epilepsy improved significantly. Our experience suggests that the combination of endovascular and surgical treatment is effective for recurrent infantile dural arteriovenous fistula.

We retrospectively examined pediatric 83 patients with pneumonia due to Mycoplasma pneumoniae, ranging in age from 6 months to 14 years, treated with tosufloxacin (TFLX) for more than 3 days between October 2010 and December 2011. The TFLX dose was 12 mg/kg/day (maximum 360 mg/day). Seventy-eight of the 83 children treated with this drug showed symptom amelioration, and the response rate to the drug was 94.0%. The remaining 5 patients showed no improvement despite drug administration for 3 to 6 days, and TFLX was switched to minocycline, which relieved symptoms. Forty-six of the 83 were given TFLX as initial treatment, and the remaining 37 not responding to clarithromycin (CAM) and azithromycin (AZM) were also treated with TFLX. This drug was effective in 41 (89.1%) of the 46 patients initially treated with TFLX and TFLX was effective in all 37 (100%) patients not responding to CAM and AZM. Side effects of TFLX included mild diarrhea, observed in 3 patients, but no patients had joint symptoms or convulsions.

The clinical effect of peramivir was examined retrospectively in 30 children aged 23 days to 8 years; they had been treated with peramivir at our hospital within 48 hours after the onset of influenza from November 2010 to April 2011. Intravenous dripping of peramivir at a dose of 10 mg/kg was performed only once for 15 to 30 minutes. To examine the clinical effect of peramivir, the time from dosing to defervescence (body temperature <37.5 degrees C) was evaluated. To compare the clinical effects of peramivir and oseltamivir, the time required for the defervescence was evaluated in a similar manner in 30 children aged 7 months to 8 years who had been treated for influenza with oseltamivir at a dose of 4 mg/kg/day. The influenza type was type A (n=25) and type B (n=5) in the peramivir group and type A (n=26) and type B (n=4) in the oseltamivir group. In the peramivir group, 5 (16.7%), 16 (53.3%), and 24 (80.0%) patients achieved defervescence within 6, 12, and 24 hours, respectively. In the oseltamivir group, 3 (10.0%) and 6 (20.0%) patients had defervescence within 12 and 24 hours, respectively. The difference between these groups was statistically significant (p<0.05). An increase in the levels of AST and ALT was observed as an adverse reaction in 1 patient. Thus, peramivir was determined to be effective to influenza in children.

We assessed the clinical efficacy of tebipenem pivoxil (TBPM-PI) in 30 children with pneumonia who, despite having received oral administration of beta-lactam antibiotics at the standard dose for at least 3 days, had no relief of symptoms and showed an abnormal shadow on the chest X-ray and elevated serum CRP levels of 3.0 mg/dl or more between December 2009 and November 2010. TBPM-PI was administered at a single dose of 4 mg/kg twice a day for 3 days. The children ranged in age from 8 months to 5 years. The serum CRP level ranged from 3.05 to 12.9 mg/dl. In 28 of the 30 children, either Streptococcus pneumoniae or Haemophilus influenzae or both were detected. Of the 28 children, 7 carried penicillin resistant S. pneumoniae; 9 carried beta-lactamase nonproducing ampicillin resistant H. influenzae; and 3 carried both. In all children, defervescence was observed within 48 hours of the start of TBPM-PI administration, and the severity of coughing/wheezing reduced significantly by the 3rd to 5th day. Thus, TBPM-PI was determined to be effective. Diarrhea or loose stool was observed as an adverse reaction in 4 children (13.3%).

An evaluation committee studied the relationship between initial treatment drug and prognosis in 339 of 466 subjects with bacterial meningitis treated at 108 institutions between April 2004 and January 2007, after excluding those with uncertain diagnosis or non-assessable records. Prognosis was considered unfavorable if meningitis sequelae such as quadriplegia, deafness, or epilepsy were present in 3- month follow-up; Based on this definition, 43 (12.7%) had a poor prognosis. No significant relationship was seen between unfavorable prognosis and age or causative pathogen. More had an unfavorable prognosis if treatment was initiated 4 days or later after onset. The percentage with an unfavorable prognosis was 6.4% (4/64) in the group administered combined panipenem/betamipron (PAPM/BP) plus ceftriaxone (CTRX), 10.5% (6/57) administered MEPM plus cefotaxime (CTX), 14.0% (7/50) administered meropenem (MEPM) plus CTRX, and none of the 23 administered CTRX alone. The percentage with an unfavorable prognosis was 26.2% (11/42) in those administered MEPM, significantly higher than that in those administered PAPM/BP plus CTRX, MEPM plus CTX, or CTRX alone (p < 0.05). We concluded that in initial treatment, it would be more desirable to use MEPM combined with another drug than alone.

Background: The efficacy and safety of a fentanyl-containing patch formulated for 1-day application at the initiation and during continuous treatment of cancer pain were evaluated in patients previously untreated with opioid analgesics., Methods: In the dose-titration period (Period I), the 1-day formulation (0.84 mg x day(-1)) was applied for 2 days. If pain relief was insufficient, the dose was titrated, and the success rate was evaluated. In the double-blind period (Period II), the efficacies of the 1-day and the 3-day formulations for pain control were compared., Results: The dose-titration success rate of the 1-day formulation was 80.6%, and its analgesic effect was comparable to that of the 3-day formulation. Moreover, tolerability of the 1-day formulation was good. Adverse events occurring in the patients were those generally seen after treatments with opioid analgesics, and severe symptoms were also reported., Conclusions: Dose titration of the 1-day formulation was accomplished in a short period in patients with cancer pain who had been previously untreated with opioid analgesics; the efficacy of the formulation for pain control after repeated dosing was comparable to that of the 3-day formulation, and its tolerability was good. However, it was considered that the 1-day formulation should be used in patients with good tolerability to opioid analgesics. Further, for safety reasons, the dose should not be increased for at least 2 days after the initial application and the last dose increase.

Background: In patients with moderate to severe cancer pain receiving treatment with opioid analgesics, the treatment was switched from the existing opioid analgesic to the 1-day fentanyl patch (the "1-day formulation"), and the efficacy and safety of the 1-day formulation were evaluated., Methods: The preceding opioid analgesic therapy was switched to therapy with the 1-day formulation, at a dose level corresponding to the daily dose level of the preceding opioid analgesic. The pain control rate was evaluated 10 days after the treatment switch. The dose level of the 1-day formulation was kept unchanged for the first 2 days after the treatment switch., Results: The pain control rate with the 1-day formulation was 81.8% (54/66 patients). In 57.6% (38/66) of patients, the treatment switch to a low-dose 1-day formulation (0.3 or 0.6 mg x day(-1)) yielded sustained pain control. The adverse reactions to the 1-day formulation observed in this study were similar to those previously reported for the Durotep MT Patch (the "3-day formulation"). No severe adverse reactions, such as respiratory depression, were noted in the present study. Thus, the 1-day formulation was well-tolerated., Conclusions: In patients with moderate to severe cancer pain, switching of opioid analgesic therapy to 1-day formulation therapy has been shown to be safe and useful, following rotation from other opioids, for controlling cancer pain. The demonstrated utility was similar to that associated with the 3-day formulation.

The minimum inhibitory concentation (MIC) and minimum bactericidal concentration (MBC) of 8 parental antibiotics were determined using 21 strains of Haemophilus influenzae from 21 children with invasive H. influenzae infection in 2006-2009. Children were from 4 months to 12 years, with 18 (85.7%) under 1 year old. Diagnosies involved meningitis or pneumonia in 7 (33.3%); epiglottitis, phlegmon, or arthritis in 2 each (9.5%), and occult bacteremia in 1 (4.8%). The capsule type was b (Hib) in 19 (90.5%). Classified by penicillin binding protein (PBP) gene mutation, strains were classified into (i) 6 beta-lactamase negative ampicillin resistant (BLNAR) (28.6%), (ii) 5 low-BLNAR (23.8%), (iii) 4 beta-lactamase positive clavulanic acid/amoxicillin resistant-II (19.0%), (iv) 2 beta-lactamase positive ampicillin resistant (9.5%), and (v) 4 beta-lactamase negative ampicillin susceptible (19.0%). Compared to a 2003-2005 survey, the number of sensitive strains had decreased significantly (p < 0.05). MIC90/MBC90 of ampicillin was 64/>128 microg/mL, piperacillin 16/>128 microg/mL, cefotaxime 0.5/0.5 microg/mL, ceftriaxone 0.12/0.12 microg/mL, panipenem 0.5/0.5 microg/mL, meropenem 0.12/0.12 microg/mL, doripenem 0.25/0.25 microg/ml, and chloramphenicil 1/2 microg/mL against H. influenza.

The cases were a 64-year-old man and a 57-year-old woman both with discomfort and dysphasia. They were given a diagnosis of esophageal achalasia after gastrointestinal endoscopy, barium esophagography and esophageal internal pressure tests. Their symptoms were dramatically improved by localized botulinum toxin injections, which were commonly available in the US. The localized botulinum toxin injection treatment is safe and minimally invasive with few complications. It is effective to reduce symptoms in esophageal achalasia.

Recurrent Group A Streptococcus (GAS) infection was defined as a case in which GAS infection was suspected during June 2006-December 2008 and GAS was detected more than 2 times by throat culture. T serotype and emn genotype were investigated for GAS bacteria isolated from children with recurrent GAS infection. Bacteria gene homology was studied using pulsed-field gel electrophoresis (PFGE). Of the 43 cases of GAS infection in 21 children used as subjects, 20 had GAS infection 2 times and one 3 times. A comparison of the first and second infection in subjects (and the second and third for the child with 3), bacteria isolated from 11 cases had coincident properties and those from the remaining 11 not-coincident. The mean period of first and second infections (second and third for the child with 3) was 29.1 +/- 17.1 days for the coincident group and 215.2 +/- 187.8 days for the not-coincident group. A significant group difference in period was seen (p = 0.0013). Ten of 12 children with recurrent GAS infection within 8 weeks of the first infection and one of 10 who had it more than 8 weeks after that were included in the coincident group, indicating a significant difference (p = 0.0028).

We investigated the efficacy of diffusion-weighed whole body imaging with background body signal suppression (DWIBS) in assessing effects of chemoradiation therapy (CRT) on rectal carcinoma. DWIBS was performed in patients (n=12) with primary rectal carcinoma undergoing preoperative CRT before and 3 weeks after the treatment. Each patient received a total irradiation dose of 45 Gy at a single dose of 1.8 Gy administered once daily. Parallel to this, in the 1st, 3rd and 5th weeks 350 mg/m2 5-fluorouracil and 35 mg/m2 l-leucovorin were administered for 5 days. The apparent diffusion coefficient (ADC) was measured by DWIBS and surgical resection of the tumors enabled a correlation of ADC values with the pathological findings. With respect to histopathological grading of regression, two, five and five cases exhibited Grade 3, Grade 2 and Grade 1, respectively. In all patients, ADC values were higher after completion of CRT compared to those before it( 1.23+/-0.26x10(-3) mm2/s vs 0.75+/-0.13x10(-3) mm2/s, p<0.001). After completion of CRT, mean ADC values were 1.71+/-0.38x10(-3) mm2/s, 1.25+/-0.10x10(-3) mm2/s and 1.02+/-0.08x10(-3) mm2/s for Grade 3, Grade 2 and Grade 1, respectively. These preliminary results indicate that DWIBS may be a valuable tool to assess effects of CRT on rectal carcinoma by using appropriate cut-off values.

Gelastic seizure is a rare form of epilepsy defined as automatic bouts of laughter without mirth commonly associated with a hypothalamic hamartoma. Surgical treatment of hypothalamic hamartomas is associated with a high risk of complications because of the close vicinity of adjacent structures such as the optic tracts and mammillary bodies. This case was an 11-year-old girl who presented with gelastic seizure and complicated partial seizure. She developed gelastic seizure at a frequency of 10 bouts per day. She was found to have an elliptical mass close to the left hypothalamus. The signal intensity on magnetic resonance imaging (MRI) was consistent with hypothalamic hamartoma. The patient underwent surgical resection by a subtemporal approach. Pathological findings confirmed the diagnosis of hypothalamic hamartoma. Postoperative MRI demonstrated that the hypothalamic hamartoma was successfully resected. Twenty four months after surgery, complicated partial seizure in this patient has improved to Engel's class 1a and gelastic seizure has improved to Engel's class IIIa.

The inpact of the International Subarachnoid Aneurysm Trial (ISAT) trial publication in 2002 and major technical advances in neuroimaging, endovascular devices and techniques have resulted in increasing numbers of patients with ruptured aneurysms undergoing endovascular coiling, as first-line treatment for aneurysm occlusion. We treated six cases of ruptured aneurysms with this strategy, with choice of clipping as as additional treatment following intentional partial coiling. In this series, patients ranged in age from 36 to 74 years and included one man and five women. Three aneurysms were located in AcomA, 1 in ACA, and 2 in MCA. The reasons for the choice of this strategy were clinical and angiographical spasm in 2, high general surgical risk in 2, and other reasons in 2 cases, respectively. The mean interval between the first partial coiling and final clipping was 33 days. All cases were successfully clipped without difficulties and coil removal were performed in 3 cases for follow up examination. It is proposed that the choice of this strategy contributes to progresses in overall outcomes in cases of aneurysmal subarachnoid hemorrhage.

We examined the frequency of ampicillin (ABPC) resistance of 3784 strains of Haemophilus influenzae isolated from the infants aged from 1 month after birth to 12 years who had been treated in the Pediatric Department of our hospital for 9 years and 6 months from July 1999 to December 2008. We determined the drug susceptibility by Etest, and judged the resistance by the standard of Clinical and Laboratory Standard Institute. The rate of strains of MIC of less than 2 microg/ml to ABPC was 87.1% in 1999, but the ratio was decreasing year after year significantly up to 28.7% in 2008 (p < 0.001). beta-lactamase negative ABPC resistant (BLNAR) strains whose MIC to ABPC was more than 4 microg/ml was 2.9% in 1999, but increased significantly to 43.3% in 2008 (p < 0.001). MIC90 was 2 microg/ml in 1999, but increased to 16 microg/ml in 2008.

A 72-year-old woman with liver cirrhosis developed spontaneous esophageal rupture due to vomiting after meals. The middle thoracic esophagus was perforated, and was, therefore, clipped endoscopically. The patient was found to have mediastinal emphysema on the chest CT image, we diagnosed as Boerhaave syndrome. The esophagus was perforated atypically. The patient was discharged in stable condition by conservative therapy. Endoscopic injection sclerotherapy may have effect that patient has not developed serious condition.

Between June 2006 and April 2007, I measured T serotypes and antibiotic susceptibilities of 367 strains of Streptococcus pyogenes isolated from children with pharyngotonsillitis in Asahikawa. Prevalent serotypes were 12 (33.8%), 1 (22.9%), and 28 (12.5%). The MIC90s of beta-lactams were 0.008 microg/ml in penicillin G, cefcapene, cefditoren, cefteram, cefdinir and faropenem, and 0.015 microg/ml in amoxicillin. Of 367 isolates, macrolide-resistant (erythromycin > 0.5 micro/ml) strains account for 42 (11.4%).

We evaluated 12 children infected with group B Streptococcus (GBS) at Asahikawa Kosei Hospital, in Japan between 1998 and 2007. The diagnosis was bacteremia in 8 and meningitis in 4. Infection occurred before day 7 in 3 patients, between days 7 and 28 in 4, and between days 29 and 131 in 5. The incidence of early onset GBS infection was 0.4 cases/1,000 live births. Four of 11 mothers were found to have GBS in antenatal culture screening. Although 2 underwent intrapartum antibiotic prophylaxis, infants suffered GBS infection. No patients with GBS infection died, but sequelae seen in 3 patients involved epilepsy and developmental delay of varying severity. The most frequent serotypes were III in 7 patients, followed by Ia in 2, Ib in 2, and II in 1. The MIC90 was 0.015 microg/mL in panipenem and imipenem, 0.03 microg/mL in meropenem, 0.06 microg /mL in cefotaxime and ceftriaxone, and 0.12 microg/mL in ampicillin. Serotypes and MICs were measured in 28 strains from pregnant women, 11 from newborns, 19 from children, and 30 from adults between May 2007 and December 2008. The frequency of serotype III in patients with GBS infection was significantly more than that in pregnant women or adults (p < 0.05). The MIC90 in these strains was the same as those of patients with GBS infection.

We report two cases treated with primary chemotherapy containing trastuzumab with a review of some important papers. The first patient was a 43-year-old female. A 33-mm left breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC) ) with several lymph node metastases in the Ax, Ic and Sc was found. After primary chemotherapy with 6 courses of EC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy for the local tumor was judged as PR. However, brain metastases appeared, so the operation was canceled. Brain metastases were then treated by gamma-knife three times, but systemic chemotherapy was not administered. Eight months later, carcinomatous meningitis appeared. Intrathecal chemotherapy with MTX+Ara-C was started, but the patient died after 20 months from the beginning of the treatment. Local efficacy was judged as CR. The second patient was a 41-year-old female. A 39-mm right breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC) ) with two lymph node metastases in the Ax was found. After primary chemotherapy with 6 courses of FEC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy was judged as PR. The operation was scheduled, but he patient wished to continue chemotherapy for cosmetic reasons. Later, because of mild tumor regrowth, we used 2 courses of vinorelbine in combination with trastuzumab. The tumor grew more, so Bp + Ax was done. The woman is alive at this writing with no recurrence.

Between October 2006 and April 2007, we enrolled 90 children with group A streptococcal infection in a prospective multicenter study. Children aged from 8 months to 12 years (6.2 +/- 2.2 years) treated with cefditoren pivoxil 9 mg/kg/day tid for 7 days were evaluated for clinical efficacy and bacterial effect at the end of therapy and were observed for the occurrence of recurrent infection and complications 4 weeks after the end of therapy. The most frequent T-types of 90 isolates were T1, T28, and T12 at 50.0%, 21.1%, and 11.1%. Of the 90, 11 did not return for follow-up. The 79 we evaluated clinical efficacy and their symptoms were ameliorated. Four still had GAS from pharyngeal swabs at the end of therapy. Isolates from them were identical to initial strains in T-type and PFGE pattern. All 78 observed within 1 month after the end of administration had no complications, but 5 had a recurrence of GAS infection. Two still had GAS from pharyngeal swabs at the end of therapy. Isolates from recurrence cases were identical to initial strains in T-type and PFGE pattern. Adverse effects were diarrhea observed in 1.

We studied the efficacy and safety of docetaxel (DOC) for elderly breast cancer patients. Between September 1997 and June 2003, five consecutive women with advanced breast cancers who were 75 years of age or older received DOC at a dose of 60 mg/m(2) every three weeks. No premedications to prevent hypersensitive reactions and fluid retention by DOC were given. The number of DOC dosages per case was 5-16 times (12 times the median) and the relative dose intensity (RDI) was 80-100% (95% of medians). Objective partial responses were observed in all patients. The median time to partial response was 21 days (range: 21-50 days). The median time to treatment failure was 12 months (range: 5-22 months). The grade and the frequency of major side effects were the following: leukocytopenia of grade 3 (80%), edema of grade 2-3 (40%), and alopecia of grade 2 (100%). It was concluded from these findings that DOC could be safely and effectively administered to elderly advanced breast cancer patients.

An 82-year-old woman who had 5 relapses of ischemic colitis was admitted with sudden lower abdominal pain. Colonoscopic examination performed on the 2nd day revealed colon cast-like stripped colonic mucosa in the lower portion of the descending colon. She was treated conservatively. After 2 weeks, ischemic colitis healed, with slight residual stenosis. Most reports of colon cast indicated that colon cast was caused by abdominal aneurysm, operation, or external wound. The only predisposing conditions in this case were arteriosclerosis of abdominal aorta and chronic constipation. Arteriosclerosis and chronic constipation might be the important risk factors of ischemic colitis with colon cast and relapsing of ischemic colitis.

Fifty isolates of Streptococcus pneumoniae and 42 isolates of Haemophilus influenzae were isolated from the blood of children admitted to pediatric wards of hospitals in subprefucture between January 1998 and December 2005. The susceptibilities were measured by a microbroth dilution method using a standard broth and a broth containing 4.5% albumin. Against S. pneumoniae, penicillin G, ampicillin, cefotaxime, ceftriaxone, panipenem, meropenem, vancomycin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used and against H. influenzae, ampicillin, piperacillin, cefotaxime, ceftriaxone, panipenem, meropenem, clavulanic acid/ amoxicillin, cefditoren, cefcapene, cefteram, faropenem and tebipenem were used. Against S. pneumoniae, tebipenem was the highest antimicrobial activity in oral antibiotics (MIC90; < or = 0.06 microg/ml) and panipenem showed the highest activity for intravenous antibiotics (MIC90; < or = 0.12 microg/ml). Against H. influenzae, cefditoren was the highest activity for oral antibiotics (MIC90; < or = 0.06 microg/ml) and meropenem showed the highest activity for intravenous antibiotics (MIC90; < or = 50.06 microg/ml). The MIC90s measured by albumin containing broth were higher than those measured by standard broth. Protein binding rates of ceftriaxone, cefditoren, and faropenem were greater than 90%, and the MIC90 of these antibiotics measured by albumin addition methods were over 4-fold higher than those measured by standard methods.

Between August 1998 and July 2005, we studied the serotypes and mutation of penicillin-binding protein (PBP) genes of 46 strains of Streptococcus pneumoniae isolated from children with invasive pneumococcal infection in Hokkaido. The clinical diagnosis was pneumonia in 16 cases, occult bacteremia in 15, meningitis in 8, upper respiratory infection in 6, and arthritis in 1. Patients ranged in age from 2 months to 9 years old. Prevalent serotypes were 6B (39.1%), 23F (17.4%) 6A (8.7%), and 19F (8.7%). The serotype coverage rate by the 7-valent pneumococcal vaccine was greater than 70% in children. Mutation of 3 genes (Penicillin-binding S. pneumoniae, PRSP) was detected in 18 isolates, mutation of 10 genes (pbp1a and pbp2x, or pbp2x and pbp2b) in 2, and of pbp2x alone in 15. PRSP was found in serotypes 6A, 6B, and 23F, and the rate of PRSP in 6A, 6B, and 23F was 75.0%, 62.5%, and 55.6%, respectively.

An 85-year-old woman suffering from an angina attack was admitted to our hospital, and diagnosed with multiple lung metastases by CT scan. Because she was extremely aged with a long disease-free period of over 12 years, and without any life-threatening state despite multiple lung metastases, she received hormonal therapy. Examestane was considered one of the most-effective hormonal drugs for metastatic breast cancer. The efficacy of the treatment was definite: the multiple metastatic lesions showed a partial response after 5 months'treatment, and reached a complete response after 10 months'treatment. After 8 months in the complete response state, CT scan revealed progressive disease. Fortunately, the lung metastatic lesions were only slowly progressive, and she has no symptoms now. There was no side effect except for complication of subdural hematoma. Examestane is considered highly effective for metastatic breast cancer and well tolerated by an aged patient like this case.

A 39-year-old man diagnosed as Crohn's disease suffered steroid induced psycosis during treatment for Crohn's disease on July 2001. He was admitted on May 2002, because of progressing high fever, abdominal pain and diarrhea. He was treated with infriximab (5mg/kg) together with mesalazine without steroid. The treatment induced rapid improvement of systematic symptoms together with laboratory data and colonoscopic findings. He kept remission for more than 10 months after a single administration of infliximab (5mg/kg). The case is suggestive of wider indication of infliximab for Crohn' s disease.