Impact of SMAD2 and MET Expression on Lymph Node Metastasis of HER2-positive Gastric Cancer Cells.

BACKGROUND/AIM: Intra-tumoral heterogeneity, which is frequently found in various types of cancers, has been suggested to play an important role in cancer progression and metastasis. The findings of our previous study suggested that p-SMAD2 and c-MET signaling might play important roles in the progression to lymph node metastasis of HER2-positive gastric cancer. In this study, we confirmed the effect of SMAD2/MET signaling in the progression of HER2-positive gastric cancer in an animal model. MATERIALS AND METHODS: NCI-N87 cells over-expressing ERBB2, SMAD2, MET were used. To confirm the role of SMAD2 and MET expression on lymph node metastasis of gastric cancer, we orthotopically injected NCI-N87 cells with or without the knockdown of both SMAD2 and MET into the gastric walls of BALBc nude mice. RESULTS: The number of metastatic lymph nodes was significantly smaller in the knockdown group compared to that in the control group. However, there was no significant difference in gastric tumor size between the two groups. CONCLUSION: SMAD2 and MET signaling might play important roles specifically in the progression to lymph node metastasis of HER2-positive gastric cancer. c-MET and SMAD2 may be useful targets for preventing lymph node metastasis in patients with HER2-positive gastric cancer.

Influencing factors of efficacy and long-term use of amrubicin in patients with small cell lung cancer.

BACKGROUND: Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy. METHODS: The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group). RESULTS: The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001). CONCLUSIONS: In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.

Differential response in patients with large cell neuroendocrine carcinoma of the lung to initial therapy: A case series.

BACKGROUND: Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non-small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established. CASES: The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non-responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non-responder group. In the non-responder group, all patients discontinued treatment due to deterioration of general condition during first-line treatment. Thus, none of them were able to start the second-line treatment. CONCLUSION: The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

[A Case of Advanced Recurrent Rectal Cancer Successfully Treated by Rechallenge Therapy with an Anti-Epidermal Growth Factor Receptor(EGFR)Drug].

The patient was a 75-year-old man who had undergone potentially curative surgery for Stage Ⅲb rectal cancer followed by resection of liver metastases. Two years after the resection of liver metastases, lung and remnant liver metastases were found. He received chemotherapy for unresectable metastatic tumors. Based on the findings of molecular and pathological examinations(RAS: wild type; BRAF: wild type; MSI: negative; HER2: negative), the following chemotherapy regimens were administered: first-line, FOLFIRI plus panitumumab(PANI); second-line, mFOLFOX6; third-line, trifluridine/tipiracil; fourth- line, regorafenib. After fourth-line treatment, he was judged to have disease progression due to the increase in his lung and liver metastases and the elevation of tumor markers. All standard regimens were refractory, but the Eastern Cooperative Oncology Group performance status was zero and a liquid biopsy for RAS still showed wild type. Therefore, rechallenge therapy with anti-epidermal growth factor receptor(EGFR)drugs, cetuximab(CET)and irinotecan(IRI), was administered 13 months after the final course of FOLFIRI plus PANI treatment. After 4 courses of CET plus IRI, the size of the 2 metastatic tumors markedly decreased and his tumor marker levels normalized.

Two families with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): case reports and literature review.

Background: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), a hereditary gastric polyposis syndrome that presents with fundic gastric polyposis, is associated with an increased risk of gastric adenocarcinoma. The four patterns of point mutation in the adenomatous polyposis coli (APC) promoter 1B region have been identified as the cause of GAPPS. GAPPS was first reported in 2012, and only 33 families with GAPPS have been reported worldwide to date. Therefore, the clinical management for GAPPS are still controversial. We herein report two unrelated GAPPS families with the same point mutation site. Case Description: Total seven patients of two families had >100 carpeting polyps in the gastric body and fundus, and one of them (69-year-old female) had gastric adenocarcinoma. As a result of germline analysis, both families harbored a point mutation (c.-192A>G) in APC promoter 1B region, previously reported in only one family. Three of seven patients underwent total gastrectomy, and others were followed-up with regular esophagogastroduodenoscopy (EGD) and biopsy every 6 months. To summarize the reported cases, total 42 patients of 35 families have developed gastric adenocarcinoma. Conclusions: This report may contribute to determining the appropriate guidelines for the clinical practice of GAPPS. When EGD reveals gastric polyposis localized to the gastric body and fundus, it is important to obtain a detailed family history and perform germline mutational analysis. And more, point mutation type of our family cases was a rare pattern, suggested that c.-192A>G pattern might be a pathogenic variant.

Candidate Oncogenes, ARHGAP4, NOS3, and OR51B5, for the Development of Scirrhous-type Gastric Cancer.

BACKGROUND/AIM: Scirrhous-type gastric cancer (SGC), one of the most intractable cancer subtypes, is characterized by rapid cancer cell proliferation and infiltration accompanied by extensive stromal fibrosis. One of the reasons for its poor prognosis may be the lack of molecular target drugs for SGC, because of the unknown driver genes. Exploration of somatic mutations in the human samples of SGC using next-generation sequencing (NGS) has been hampered by abundant fibrous tissues in these samples. Therefore, this study aimed to determine a novel oncogene by RNA-sequencing using SGC cell lines, avoiding contamination with fibrosis. MATERIALS AND METHODS: In silico analysis of RNA-sequencing public data of the gastric cancer cell line, and RNA- sequencing using five of our unique SGC cell lines, OCUM1, OCUM2MLN, OCUM8, OCUM12, and OCUM14 were performed. RESULTS: We found three differentially expressed genes, ARHGAP4, NOS3, and OR51B5 that are significantly over-expressed in SGC cells. Immunohistochemical analysis indicated that the protein expression levels of these three genes were significantly higher in SGC than in other types of gastric cancer. The prognosis of patients with positive expression of these three genes was significantly poorer than those with negative expression. In particular, ARHGAP4 expression was an independent predictor of poor prognosis and recurrence. CONCLUSION: ARHGAP4, NOS3, and OR51B5 may be candidate driver genes for SGC. ARHGAP4 may be a promising molecular target for SGC.

Early recurrence factors in patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND: The clinical characteristics and risk factors for cancer recurrence have not been well evaluated regarding early recurrence in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) who receive concurrent chemoradiotherapy (CRT). The aim of this study was to determine the clinical characteristics and risk factors of patients with stage III unresectable LA-NSCLC treated with CRT who developed early recurrence. METHODS: We retrospectively reviewed the clinical records of 46 patients diagnosed with stage III unresectable LA-NSCLC treated with CRT at our center between July 2012 and July 2021. A tumor proportion score (TPS) < 50% was defined as "low expression" and a TPS > 50% was defined as "high expression." RESULTS: A total of 17 (37.0%) patients had a confirmed recurrence within 1 year of treatment. More patients had a lower body mass index in the early recurrence group than in the later recurrence group (p = 0.038). A higher number of patients in the late recurrence group underwent surgery after CRT (p = 0.036). Patients with a higher TPS were more likely to experience late recurrence than early recurrence (p = 0.001), whereas more patients with stage N3 disease were in the early recurrence group (p = 0.011). Multivariate analysis identified lower TPS expression as an independent risk factor for early recurrence after CRT. Overall survival was prolonged in the late recurrence group (p < 0.001). CONCLUSIONS: A lower TPS may be a predictor of early recurrence after CRT in patients with LA-NSCLC. These patients should be closely monitored for post-treatment recurrence.

The safe removal of a superior mediastinal foreign body by mediastinoscopy: a case report.

BACKGROUND: Mediastinal foreign bodies might cause mediastinal organ injury or mediastinal abscess. The prompt removal surgery of mediastinal foreign bodies is needed to prevent those complications. We report a case in which a mediastinal foreign body was removed by video-mediastinoscopy. CASE PRESENTATION: The patient, a 74-year-old man with a chief complaint of hoarseness, was referred to our department for surgical management of a wooden foreign body that had traumatically migrated into the superior mediastinum. During the surgery, the video-mediastinoscopy was introduced under the pneumomediastinal pressure. We could dissect the scar tissue and remove the azalea tree branch safely and carefully, without damaging the other mediastinal organs. He was discharged on postoperative day 5, with no complications. CONCLUSIONS: Video-mediastinoscopic approach under pneumomediastinal pressure is minimally invasive and could provide wide surgical view. Therefore, we consider it useful and effective for removal of foreign bodies in the mediastinum.

Bilateral Distal Transradial Approach for Coiling of Basilar Artery Aneurysm: A Technical Note.

Distal transradial approach (dTRA) for neuroendovascular procedures has received much attention in recent years as a newer and less invasive alternative to the conventional transfemoral or transradial approaches. We present the case of an 89-year-old woman with a basilar artery aneurysm requiring simultaneous catheterization of the bilateral vertebral arteries who was successfully embolized using bilateral dTRA. The aneurysm was accessed from the right vertebral artery using the right dTRA. Control angiograms during the procedure were performed from the left vertebral artery via the left dTRA. The operator's posture was ergonomically comfortable, and the catheters were easy to handle during the procedure. To the best of our knowledge, this is the first case of a bilateral dTRA used for neuroendovascular procedures. Bilateral dTRA is a safe and minimally invasive method for patients and ergonomically comfortable for operators.

Efficacy and predictors of rechallenge with immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs. METHODS: We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021. RESULTS: Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059). CONCLUSIONS: Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control.

Risk factors for acute exacerbation in lung cancer complicated by interstitial lung disease with slight reticular shadows.

BACKGROUND: The risk of cancer treatment-related acute exacerbation (AE) in patients with lung cancer and mild interstitial lung disease (ILD) on imaging, classified as indeterminate for usual interstitial pneumonia (UIP), has not previously been clarified. METHODS: We retrospectively reviewed the clinical records of 27 patients with lung cancer and ILD who were diagnosed and treated from April 2016 to March 2021. RESULTS: Among the 27 patients, 21 were classified as indeterminate for UIP and six as UIP/probable UIP; furthermore, 10 (46.6%) and three (50%) patients from each group, respectively, developed treatment-related AEs. No significant difference was observed regarding the incidence of AEs between the two groups. However, significantly more patients in the AE group received immune checkpoint inhibitors (ICIs) compared to the non-AE group (p = 0.021). Multivariate analysis revealed that the use of ICIs was a significant independent risk factor for treatment-related AEs. CONCLUSIONS: Lung cancer patients with mild ILD suggestive of indeterminate for UIP and UIP patterns are at an increased risk for treatment-related AEs. Furthermore, ICI use is an independent risk factor for AEs in patients with lung cancer complicated by ILD, and ICIs should be used with great caution.

A Case of Hemorrhagic Cholecystitis and Hemobilia Under Anticoagulation Therapy.

BACKGROUND Hemorrhagic cholecystitis is a rare disease which can be fatal in some cases. Hemorrhagic cholecystitis can sometimes be confused with common biliary diagnoses, as its symptoms imitate other hepatobiliary diseases. We report a case of hemorrhagic cholecystitis with hemobilia caused by the administration of anticoagulant agents. CASE REPORT A 70-year-old man was admitted with abdominal distention and pain. Ultrasound (US) and computed tomography (CT) showed a distended and wall-thickened gallbladder with hyperdense materials. Based on these findings and the laboratory data, the patient was diagnosed with acute cholecystitis with cholangitis. Because the patient's hemodynamics were stable, endoscopic retrograde cholangiopancreatography (ERCP) was performed first to improve the bile flow. The results of ERCP showed blood from the common bile duct by cannulation, which was suspected to reflect hemorrhagic cholecystitis. As the abdominal symptom and CT findings worsened on the day after ERCP, emergency laparoscopic cholecystectomy was performed. An examination of the specimen revealed ulcer formation on the mucosal side of the gallbladder. The patient was discharged 6 days after the operation without any surgical complications. CONCLUSIONS ERCP and early laparoscopic cholecystectomy were performed for a patient with hemorrhagic cholecystitis and hemobilia. Early diagnosis and treatment can lead to good outcomes in patients with hemorrhagic cholecystitis. Since the number of patients who are taking antithrombotic agents is increasing, hemorrhagic cholecystitis should be considered when any unusual imaging findings associated with cholecystitis are observed.

[Two Cases of Advanced and Recurrent Gastric Cancer with Long-Term Survival Due to Successful Chemotherapy].

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.

A case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis.

A 53-year-old woman was referred to our hospital for detailed examination of abnormal chest shadows recognized on CT imaging. Transbronchial lung biopsy of a right S6 nodular shadow led to a diagnosis of lung adenocarcinoma. FDG-PET-CT showed FDG accumulation in the Th11 and L2 vertebral bodies and osteoblastic bone lesions. Since osteoblastic bone metastasis in lung cancer is extremely rare, CT-guided bone biopsy was performed. The tumor was diagnosed as ROS1-rearranged lung adenocarcinoma, for which crizotinib was administered, which led to improvement of both the primary and metastatic lesions. We report here a rare case of ROS1-rearranged lung adenocarcinoma with osteoblastic bone metastasis of lung cancer.

Primary pulmonary T-cell lymphoma with lung adenocarcinoma: a case report.

BACKGROUND: Primary pulmonary T-cell lymphoma is an extremely rare disease that is characterized by neoplastic proliferation of T-cell lymphocytes in the lung. CASE PRESENTATION: An 88-year-old Japanese woman was admitted to our hospital because of dyspnea. She was treated with antibiotics for chest x-ray findings of consolidation in the upper and middle lobes of the right lung. However, her condition worsened and progressed to respiratory failure, which led to death 14 days after admission. Autopsy of the lungs revealed both T-cell lymphoma and adenocarcinoma. CONCLUSIONS: Our patient had a rare case of primary pulmonary T-cell lymphoma with primary lung adenocarcinoma. Further evidence and accumulation of case reports are required to clarify the pathophysiology of primary pulmonary T-cell lymphoma.

Exogenous gene transfer of Rab38 small GTPase ameliorates aberrant lung surfactant homeostasis in Ruby rats.

BACKGROUND: Rab38 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab38 and other gene mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells. METHODS: A replication-deficient recombinant adenovirus expressing rat Rab38 (Ad-Rab38) was constructed. Alveolar type II cells were isolated from the LEC rats and tested for lung surfactant phosphatidylcholine secretion. The rats were also examined whether exogenous expression of Ad- Rab38 could rescue the altered lung surfactant homeostasis in the lungs. RESULTS: Isolated type II cells infected with Ad-Rab38 exhibited improved secretion patterns of [3H]phosphatidylcholine, i.e. increased basal hyposecretion and decreased agonist-induced hypersecretion. Endobronchial administration of Ad-Rab38 improved the morphology of type II cells and lamellar bodies, reducing their sizes close to those of wild-type rats. The increased amounts of phosphatidylcholine and surfactant protein B in the lamellar body fractions were decreased in the Ad-Rab38 infected lungs. CONCLUSIONS: These results provide strong evidence that the aberrant lung surfactant homeostasis in the LEC rats is caused by Rab38 deficit, and suggest that endobronchial delivery of the responsive transgene could be an effective method to ameliorate the abnormal lung phenotype in the animal model of HPS.

The anti-overactive bladder activity of KW-7158 is mediated by blocking equilibrative nucleoside transporter-1.

KW-7158 is a novel therapeutic candidate for treating overactive bladder (OAB) with a unique mode of action: suppression of sensory afferent nerves. However, the molecular target of this compound remains unknown. We herein report the identification of the KW-7158 target to be equilibrative nucleoside transporter-1 (ENT1). A membrane protein expression library of ca. 7000 genes was expressed in a dorsal root ganglion cell line, which we had previously generated, and subjected to screening for binding with a fluorescent derivative that retains high binding activity to the target. The screening revealed that only cells transfected with an ENT1 expression vector exhibited significant binding. We next performed [(3)H]KW-7158 binding experiments and an adenosine influx assay and found that KW-7158 binds to and inhibits ENT1. To further demonstrate the pharmacological relevance, we evaluated other known ENT1 inhibitors (nitrobenzylthioinosine, dipyridamole, draflazine) in an in vitro bladder strip contraction assay and the rat spinal cord injury OAB model. We found that all of the inhibitors exhibited anti-OAB activities, of which the potencies were comparable to that of adenosine influx inhibition in vitro. These studies demonstrated that the pharmacological target of KW-7158 is ENT1, at least in the rat OAB model. Our results will aid understanding of the precise mechanism of action of this drug and may also shed new light on the use of the adenosine pathway for the treatment of OAB.

[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture and the northern district of Aichi prefecture--2009].

High pathogenicity and drug resistance of Streptococcus pneumoniae are serious problem in clinical practice. Since 1999, we have conducted epidemiologic analyses of S. pneumoniae in Chubu district. We report the results of the analysis conducted in 2009. Three hundred and eight (308) S. pneumoniae isolates with a gene coding for autolysin lyt-A, which had been isolated from patients at 21 medical institutions in Gifu prefecture and the northern part of Aichi prefecture in 2009, were enrolled in this study. The strains were classified according to their drug resistance based on the presence of the pbp mutation, and examined for the presence of the two macrolide-resistance genes, ermB and mefA. Moreover, they were serotyped using type-specific antisera. The mean age of the patients from whom these S. pneumoniae strains were isolated, was 23.4 +/- 30.1 years old, and children aged 15 years old or less accounted for 66% of all the patients. Genotype penicillin-susceptible S. pneumoniae (gPSSP), genotype penicillin-intermediate S. pneumoniae (gPISP) and genotype penicillin-resistant S. pneumoniae (gPRSP) were 22 (7.1%), 131 (42.5%) and 155 (50.3%), respectively. The strains with mefA positive and ermB negative, mefA negative and ermB positive, and mefA positive and ermB positive were 80 (26.0%), 153 (49.7%), and 47 (15.3%), respectively. The MIC90 values of tebipenem (TBPM) and faropenem were 0.06 microg/mL and 0.5 microg/mL, respectively. TBPM showed the high bactericidal activity against gPRSP. In carbapenems, panipenem and biapenem exhibited higher bactericidal activities. Quinolone-resistant S. pneumoniae (QRSP) were isolated from 10 (3.2%). QRSP dominated 5 (7.9%) and 3 (1.5%) among the elderly (over 65 years old) and children, respectively. (As for the serotype, serotypes 6, 19 and 23 were 60 (19.5%), 62 (20.1%), and 44 (14.3%), respectively. Further epidemiologic studies on S. pneumoniae might be required also in the future, including the relationship between the serotype and drug resistance.

[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture].

Since antimicrobial resistance in Streptococcus pneumoniae become serious problem, we have conducted the epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture. We have investigated the mutations of penicillin-binding protein (PBP) cording genes, the mutations of macrolide-resistant cording genes, and antimicrobial susceptibility using broth microdilution method, for 345 strains isolated from clinical specimens between May 2006 and July 2006 at 12 clinical facilities of 5 medical area. The ratio of penicillin-susceptible S. pneumoniae (gPSSP), penicillin-intermediate S. pneumoniae (gPISP), and penicillin-resistant S. pneumoniae (gPRSP), which were judged by molecular techniques, were 7.2%, 53.5%, and 39.4%, respectively. Only 1 gPSSP strain was isolated from children under three years old. There have been regional differences of the isolation rate of gPRSP between Gifu/Chuno area (55-60%) and Tono/Hida area (23-32%) in second- or third-medical facilities. The isolation rate of PBP mutation genes, pbp2x, pbp1a and pbp2b, were 92.8%, 52.5% and 53.3%, respectively. The isolation rate of macrolide-resistant cording genes, mefA only, ermB only, and both mefA and ermB, were 30%, 50% and 8%, respectively. The strains of S. pneumoniae with both mefA and ermB mutations, increased from 4% in 2002 to 8% in 2006. The antimicrobial susceptibility of S. pneumoniae to penicillin G (PCG) showed two peaks around 0.03 and 1 microg/mL, and 89% of S. pneumoniae with minimum inhibitory concentration (MIC) value 1 microg/mL was gPRSP. The MIC values of PCG against 69% strains of gPRSP distributed between 0.25 and 1 microg/mL. There have been the decreased tendency for the differences among medical facilities in penicillin resistant strains. Although cefditoren showed the most effective antimicrobial activity in oral cephems tested, there have been the strains with MIC value of over 1 microg/mL. The MIC90 of panipenem was 0.125 microg/mL, which was the best antimicrobial activity in carbapenems. The resistant rates of clarithromycin and azithromycin were 85% and 84%, respectively. The strains with the gene mutation of ermB have showed resistant to clindamycin. The MIC90 of tosufloxacin was 0.25 microg/mL, which was the best antimicrobial activity in quinolones. We have detected 4 levofloxacin highly resistant S. pneumoniae, of which MIC value was over 32 microg/mL. Also, we have encountered the episode of the spread of S. pneumoniae in one family, which was clarified by scientific approach.

Combination therapy with intraventricular interferon-alpha and ribavirin for subacute sclerosing panencephalitis and monitoring measles virus RNA by quantitative PCR assay.

Subacute sclerosing panencephalitis (SSPE) is a degenerative disease of the central nervous system that leads to death within a few years. Recently, it has been reported that combination therapy with intraparenchymal interferon-alpha (INF-alpha) and intraventricular ribavirin is effective. An 11-year-old SSPE patient whose clinical symptoms progressed rapidly, was treated first with intraventricular INF-alpha and then with combined intraventricular INF-alpha and ribavirin therapy. To monitor viral load over the course of the therapy, measles virus RNA was quantified using a real-time polymerase chain reaction assay. Measles virus RNA decreased rapidly after the INF-alpha therapy was started, paralleling the decrease in the measles antibody titer in the cerebrospinal fluid and the improvement in the neurological disability. After intraventricular ribavirin was combined with INF-alpha therapy, no further improvement was observed. The neurological disability gradually progressed, although the amount of virus RNA remained low.