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This study aimed to evaluate the uptake of the clinical effectiveness of [S-methyl

Long-term outcomes after surgical resection of bile duct cancer remain unsatisfactory, and survival, particularly after tumor recurrence, is poor. Gemcitabine and cisplatin combination (GC) therapy is the standard first-line treatment; however, second-line approaches are yet to be established. Radiotherapy may prolong the survival of patients with advanced biliary tract cancer, and particle radiotherapy delivers a more concentrated dose than conventional radiotherapy to deeper tumors. The present report describes the long-term survival of a 65-year-old man with distal bile duct cancer of pathological stage IIA (T2N0M0; depth of invasion, 5.5 mm) following multimodal treatment. Following subtotal stomach-preserving pancreatoduodenectomy, multiple hepatic recurrences were identified 9 months later, and GC therapy was initiated. The tumors were no longer evident 18 months later, and GC therapy was discontinued at the patient's request. A computed tomography (CT) scan performed 30 months after surgery identified a new solitary hepatic recurrence and duke pancreatic monoclonal antigen type-2 (DUPAN-2) levels were increased. Further GC therapy was declined. Carbon ion radiotherapy (CIRT) at a dose of 60 Gy [relative biological effectiveness (RBE)-weighted absorbed dose] was then delivered in four fractions over 4 days [15 Gy (RBE)/day]. Tumor size decreased on CT, and fluorodeoxyglucose-positron emission tomography/CT revealed a decline in the standardized uptake value of the tumor after 2 months, with decreased DUPAN-2 levels. Following regrowth of the hepatic recurrence, CIRT was repeated at a dose of 66 Gy (RBE) in four fractions over 4 days [16.5 Gy (RBE)/day] and stable disease was maintained for 19 months. After 19 months, CT revealed tumor regrowth and another new metastatic lesion was identified in the left kidney. The patient received systematic chemotherapy again and died of the disease 81 months after the initial surgery. In conclusion, CIRT is a potential treatment option to control solitary recurrence of biliary tract cancer.

Dehydrative allylation between widely available aldehydes and allylic alcohols to afford β,γ-unsaturated ketones was enabled by a synergistic merger of a thiazolium N-heterocyclic carbene catalyst and a palladium-bisphosphine catalyst.

Aim Evaluation of the therapeutic efficacy of carbon-ion radiation therapy for isolated lymph node recurrence following curative resection of esophageal cancer. Materials and methods Ten cases with lymph node recurrence after esophageal cancer surgery were treated with carbon-ion radiation therapy. A total of 48.0 Gy [relative biologic effectiveness (RBE)] was delivered over 3 weeks with a daily dose of 4.0 Gy (RBE). Results The median follow-up duration was 27.1 months (range=3-92.0 months) after carbon-ion radiation therapy. The local control rates at 2, 3 and 5 years were 92.4%. The overall survival rates at 2, 3 and 5 years were 70.0%, 58.3% and 21.9%. The median survival period was 45.3 months after carbon-ion radiation therapy. There were no toxicities of grade 3 or higher. Conclusion Carbon-ion radiation therapy may be a safe and effective treatment option for isolated lymph node recurrence after radical surgery for esophageal cancer.

Treatment of the benzylallene-internal alkynes with [RhCl(CO)2]2 effected a cycloisomerization via a Csp2-H bond activation to produce the tricyclo[9.4.0.03,8]pentadecapentaene skeleton. The reaction mechanism via formation of the rhodabicyclo[4.3.0] intermediates and σ-bond metathesis between the Csp2-H bond on the benzene ring and the Csp2-RhIII bond was proposed. In addition, a plausible alternative mechanism for the previously reported cycloisomerization of the benzylallene-terminal alkynes could also be proposed. © 2017 American Chemical Society., Embargo Period 12 months

BACKGROUND The objective of this study was to evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) in patients with hepatocellular carcinoma (HCC) with stepwise dose escalation and hypofractionation in 2 combined prospective trials. METHODS Sequential phase 1/2 (protocol 9603) and phase 2 (protocol 0004) trials were conducted for patients with histologically proven HCC. The phase 1 component of protocol 9603 was a dose-escalation study; CIRT was delivered in 12, 8, or 4 fractions. After determination of the recommended dose, 2 phase 2 trials were performed in an expanded cohort, and the data were pooled to analyze toxicity, local control, and overall survival. RESULTS In the phase 1 component of protocol 9603, 69.6, 58.0, and 52.8 Gy (relative biological effectiveness [RBE]) in 12, 8, and 4 fractions, respectively, constituted the maximum tolerated doses, and 52.8 Gy (RBE) in 4 fractions was established as the recommended dose regimen for the 2 phase 2 studies. In 124 patients with a total of 133 lesions, few severe adverse effects occurred, and local-control and overall survival rates at 1, 3, and 5 years were 94.7% and 90.3%, 91.4% and 50.0%, and 90.0% and 25.0%, respectively; this included 1-, 3-, and 5-year local-control rates of 97.8%, 95.5%, and 91.6%, respectively, in the phase 2 study. In a multivariate analysis, Child-Pugh class B and the presence of a tumor thrombus were significant factors for mortality. CONCLUSIONS The safety and efficacy of CIRT in 12, 8, and 4 fractions were confirmed, with 52.8 Gy (RBE) in 4 fractions established as the recommended treatment course for eligible HCC patients. Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

SummaryVepris verdoorniana(Rutaceae) has long been regarded as a widespread and variable species occurring from Guinea to Gabon. Recent evidence has shown that the original material from the type locality in Cameroon consists of two different species,V. verdoornianain the strict sense, endemic to Lower Guinea (Cameroon, Gabon and C.A.R. in W-C Africa) andV. letouzeyiOnana, which was thought to occur from Guinea to Cameroon. In this paper we show that the West African (Upper Guinea) material previously referred to asV. letouzeyi/V. verdoornianais separate morphologically from that in Cameroon (Lower Guinea). In fact the West African material referred to comprises two distinct species, here described asV. occidentalisCheek & Onana (Guinea to Ghana, but probably extending to Benin) a tree of lowland marginal dry evergreen and semi-deciduous forest, andV. ferCheek, a species restricted to four mainly lower submontane forest locations on iron substrates in Liberia and Sierra Leone (also Upper Guinea).Vepris occidentalisis here assessed as Least Concern due to its wide range and high frequency, whilstV. feris assessed as Endangered due to the low number of locations and threats from iron ore mining projects. Both new species are illustrated and mapped.

A highly chemo- and regioselective partially intramolecular rhodium(I)-catalyzed [2+2+2] cycloaddition of allenynes with alkynes is described. A range of diverse polysubstituted benzene derivatives could be synthesized in good to excellent yields, in which the allenynes served as synthetic equivalent to the diynes. A high regioselectivity could be observed when allenynes were treated with unsymmetrical alkynes.

Treatment of the allenylazetidine-alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)propane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C-C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved.

The aims of this study were to clarify the safety and efficacy of 12-fraction carbon-ion radiotherapy (CIRT) for primary renal cell carcinoma (RCC) and to confirm the recommended dose in a prospective clinical trial. This clinical trial was planned as a non-randomized, open-label, single-center phase I/II study of CIRT monotherapy. The incidence of acute adverse events was the primary endpoint. Dose-limiting toxicities (DLTs) were defined as grade ≥3 skin, gastrointestinal tract, or urologic adverse events. Based on the eligibility criteria, 8 patients with primary RCC, including 3 medically inoperable patients and 5 patients with tumors >4 cm, were enrolled. Of the 8 patients, 5 were treated with 66 Gy (relative biological effectiveness [RBE]), and subsequently, the dose was escalated to 72 Gy (RBE) for the remaining 3 patients. The median follow-up time was 43.1 months. No DLTs were observed at any dose level though the end of follow-up. Although 1 patient died of pneumonia 3 months after CIRT, which was determined to be unrelated to CIRT, no grade 3 or higher adverse events were observed, and both local control and cancer-specific survival rates were 100%. In conclusion, the safety and efficacy of CIRT hypofractionation using 12-fractions for the treatment of eligible RCC patients, including those with inoperable or tumor size >4 cm, were confirmed in this prospective trial, and a recommended dose of 72 Gy (RBE) was established.

Tuberculosis remains a serious health problem worldwide. Patients with tuberculosis who also require nursing care due to aging and underlying diseases are considered to have a high mortality rate, however, there are few studies describing detailed examinations of such disease conditions. Objective: The present study was conducted to investigate differences in clinical features of elderly tuberculosis patients according to the levels of nursing and healthcare required. Design: The study participants included 146 elderly (&ge, 65 years) patients diagnosed with active tuberculosis among patients hospitalized with tuberculosis at a single center. The patients were classified into two groups: a nursing- and healthcare-associated tuberculosis group (n = 71) and a community-acquired tuberculosis group (n = 75). Results: The nursing- and healthcare-associated tuberculosis patients were older and had a higher frequency of comorbidities compared with the community-acquired tuberculosis group. Patients in the nursing- and healthcare-associated tuberculosis group had markedly lower levels of serum albumin and hemoglobin, and higher levels of C-reactive protein. The rate of in-hospital death was significantly higher in the nursing- and healthcare-associated tuberculosis group. This was attributed to malnutrition and comorbid conditions rather than the severity of tuberculosis. Conclusion: The prognosis was poor in elderly tuberculosis patients receiving nursing and healthcare.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.

Keetia susu Cheek and K. futa Cheek from the Republic of Guinea, and K. abouabou Cheek from Ivory Coast are described here. Each species is assessed using the IUCN standard as, respectively, Vulnerable, Endangered and Critically Endangered. Each species is illustrated and mapped. A key to the 16 species of Keetia in West Africa (Senegal to Benin) is provided. The number of species of Keetia currently accepted is now known to total 35.

The synthesis of a carbon analogue of scytonemin was accomplished on the basis of molybdenum-mediated intramolecular double Pauson-Khand type reaction of bis(allenyne), followed by the double aldol condensation of the formed double Pauson-Khand type adduct.

Treatment of the benzylallene-internal alkynes with [RhCl(CO)

The first total synthesis of (+)-sieboldine A was completed starting from 5-(p-methoxybenzyloxy)pentyne in 19 steps. The enantioselective Keck allylation provided the dienyne derivative, which was exposed to the Pauson–Khand conditions to afford the bicyclo[4.3.0]nonenone derivative with high stereoselectivity with an ee value of 93%. The following Ueno–Stork reaction formed the cis-hydrindane core with a quaternary carbon center. The late-stage Schmidt glycosylation led to the formation of the N-hydroxyazacyclononane ring.

Amplitude-based gating aids treatment planning in scanned particle therapy because it gives better control of uncertainty with the gate window. We have installed an X-ray fluoroscopic imaging system in our treatment room for clinical use with an amplitude-based gating strategy. We evaluated the effects of this gating under realistic organ motion conditions using 4 DCT data of lung and liver tumors. 4 DCT imaging was done for 24 lung and liver patients using the area-detector CT. We calculated the field-specific target volume (FTV) for the gating window, which was defined for a single respiratory cycle. Prescribed doses of 48 Gy relative biological effectiveness (RBE)/fraction/four fields and 45 Gy RBE/two fractions/two fields were delivered to the FTVs for lung and liver treatments, respectively. Dose distributions were calculated for the repeated first respiratory cycle (= planning dose) and the whole respiratory data (= treatment dose). We applied eight phase-controlled rescannings with the amplitude-based gating. For the lung cases, D95 of the treatment dose (= 96.0 ± 1.0%) was almost the same as that of the planning dose (= 96.6 ± 0.9%). D(max)/D(min) of the treatment dose (= 104.5 ± 2.2%/89.4 ± 2.6%) was slightly increased over that of the planning dose (= 102.1 ± 1.0%/89.8 ± 2.5%) due to hot spots. For the liver cases, D95 of the treatment dose (= 97.6 ± 0.5%) was decreased by ∼ 1% when compared with the planning dose (= 98.5 ± 0.4%). D(max)/D(min) of the treatment dose was degraded by 3.0%/0.4% compared with the planning dose. Average treatment times were extended by 46.5 s and 65.9 s from those of the planning dose for lung and liver cases, respectively. As with regular respiratory patterns, amplitude-based gated multiple phase-controlled rescanning preserves target coverage to a moving target under irregular respiratory patterns.

Transmetalation between [CpFe(CO)2I] and arylzinc iodide-lithium chloride complexes proceeds in the presence of catalytic amounts of palladium acetate and N,N,N’,N’-tetramethyl-1,2-cyclohexanediamine to yield the corresponding aryliron complexes [CpFe(CO)2Ar]. Phenylation of [CpFe(CO)2I] also takes place when triphenylindium is used under similar conditions. Arylboronic acids undergo arylation in the presence of cesium carbonate and a palladium-N-heterocyclic carbene complex, PEPPSI. The present methods are useful for the facile synthesis of various functionalized [CpFe(CO)2Ar]. The products [CpFe(CO)2Ar] represent an interesting class of aryl metals that undergo several transformation.

With synovial sarcoma (SS) of the thorax, being exceptionally rare, its definite diagnosis is difficult, and the optimal therapy has not yet been established. An examination of our patient, a 64-year-old man with SS using a chest roentgenogram showed a large mass with homogeneous density in the lower two-thirds of the left hemithorax. A computed tomographic image of the chest revealed a large, heterogeneous, enhanced mass in the left hemithorax. Histologic examination of the resected tumor tissues suggested monophasic fibrous SS. A fragment of the SYT-SSX1 fusion transcript, which was smaller than the control, was amplified with reverse transcriptase polymerase chain reaction. Direct sequence analyses revealed the fusion between exon 9 of SYT and exon 5 of SSX1 instead of fusion between exon 10 of SYT and exon 6 of SSX1, which is found in most cases. Although the biological and clinical significance of this rare variant is not yet known, our data present another example of the usefulness of molecular analyses for making a definite diagnosis of SS in unusual sites.

背景．Pleomorphic carcinomaは肺原発悪性腫瘍の約0.3％とされている稀な疾患である．今回我々は空洞像を呈したPleomorphic carcinomaの1例を経験したので報告する．症例．62歳，男性．主訴は咳嗽．2ヶ月前より主訴あり，精査することとなった．胸部X線で左上肺野に異常陰影を認め，胸部CTでは左上葉に壁が不整な4 cm大の空洞性病変がみられた．気管支鏡下肺生検で非小細胞肺癌と診断を得たため，左肺上葉切除及び肺門縦隔リンパ節郭清術を施行した．病理組織所見では扁平上皮癌と紡錘細胞，巨細胞が混在して増殖しておりPleomorphic carcinomaと診断された．リンパ節転移は認められず病理病期はpT2N0M0，Stage IBであった．術後8ヶ月再発の兆候はみられていない．結論．本腫瘍は他の組織型と比較して予後不良との報告もあるため厳重な経過観察が必要であると考えられる．

Carbon ions/Charged particles/Dose distribution/RBE/Clinical study. In 1994 a Phase I/II clinical study on carbon ion radiotherapy was begun at NIRS using HIMAC, which was then the world’s only heavy ion accelerator complex dedicated to medical use in a hospital environment. Among several types of ion species, we have chosen carbon ions for cancer therapy because they had the most optimal properties in terms of possessing, both physically and biologically, the most effective dose-localization in the body. The purpose of the clinical study was to investigate the efficacy of carbon ion radiotherapy against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. The RBE of carbon ions was estimated to be 2.0 to 3.0 along the SOBP for acute skin reactions. As of August 2006, a total of 2,867 patients had been entered into Phase I/II or Phase II studies and analyzed for toxicity and local tumor response. The results have shown that carbon ion radiotherapy has the potential ability to provide a sufficient dose to the tumor with acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors and those with histologically non-squamous cell type of tumors such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the biological and physical properties of high-LET radiation, the efficacy of treatment regimens with small fractions in short treatment times has been confirmed for almost all types of tumors in carbon ion radiotherapy.

Heavy carbon-ion beam therapy has revealed several potential advantages over X-rays. Heavy-ion therapy has been applied for various solid tumors including esophageal squamous cell carcinoma (SCC). Although the local control rate of carbon ion radiotherapy for esophageal cancer has revealed better rates than that of conventional radiotherapy, some patients have shown resistance to the treatment. No study has evaluated whether anti-cancer drugs can enhance the anti-tumor effect of heavy carbon-ion beam irradiation. Therefore, we evaluated the efficacy of docetaxel, fluorouracil, cisplatinum, doxorubicin and gemcitabine to enhance the anti-tumor effects of heavy carbon-ion beam irradiation on human esophageal SCC cells in both in vitro and in vivo experiments. Fluorouracil, cisplatinum, doxorubicin and gemcitabine showed only additive anti-tumor effects. On the other hand, growth suppression was significantly potentiated by the combined treatment with heavy carbon-ion beam and docetaxel as compared to that treated with either agent alone. These data suggest that heavy carbon-ion beam irradiation combined with docetaxel may be a potentially useful therapeutic strategy for locally advanced esophageal SCC.

Objective: The purpose of this study is to clarify the efficacy and toxicity of hyperfractionated radiation therapy (RT) for patients with nasopharyngeal cancer (NPC). Methods: Twenty-two patients with NPC treated at our hospital between April 1994 and December 2002 were the subjects of this study. They received hyperfractionated RT with a fraction size of 1.2 Gy, with a median tumor dose of 72 Gy (range 64.8-80.4). During this study period, our institutional strategy for locoregionally advanced NPC included neoadjuvant or concurrent chemotherapy combined with hyperfractionated RT, and 17 patients received some forms of cisplatin-containing chemotherapy. Results: With a median follow-up of 59 months, the estimated 5-year disease-free survival rate and overall survival rate were 72.7 and 85.2%, respectively. Acute hematological toxicities were acceptable and manageable. However, >50% of patients required nutritional support, and experienced severe pharyngitis, skin reaction and body weight loss. With regard to late sequelae, one patient developed grade 3 osteomyelitis, and one patient each developed grade 4 passage disturbance and laryngeal edema. No patients experienced any grades of optic nerve injury or temporal lobe necrosis. Conclusions: Hyperfractionated RT using 1.2 Gy per fraction, for a total dose of 72 Gy, produces a comparable treatment outcome. Although deleterious neurological sequelae were not observed in this study, caution should be exercised regarding other late sequelae, such as osteomyelitis and passage disturbance.

Previously, we conducted a nationwide survey of primary central nervous system lymphoma (PCNSL) treated between 1985 and 1994 in Japan. In the present study, we conducted further investigations of PCNSL patients treated between 1995 and 1999 to clarify possible changes with time in the clinical features, treatment, and outcome of this disease. Thirteen Japanese institutions were surveyed, and data on 101 patients with histologically-confirmed PCNSL were collected. These data were compared with those of 167 patients treated at the same institutions between 1985 and 1994. Regarding patient and tumor characteristics, the proportion of patients with good performance status (PS) was significantly higher in the group treated during 1995–1999 than in that treated during 1985–1994, but other characteristics were not significantly different. Regarding treatment, more patients in the more recent period (66%) received systemic chemotherapy than those in the preceding period (53%, P = 0.049). For all patients, including those who did not complete radiotherapy, the median survival time was 17 months and 30 months in patients treated between 1985 and 1994 and those treated between 1995 and 1999, respectively, and the 5-year survival rate was 15% versus 31% (P = 0.0003). In both patient groups, higher age and tumor multiplicity were associated with poor prognosis in multivariate analysis. In patients treated between 1995 and 1999, those who received systemic chemotherapy showed significantly better prognosis than those who did not (P = 0.0049), but the difference was not significant in multivariate analysis (P = 0.23). The high survival rates observed in the present survey are comparable with those of recent prospective studies employing intensive chemoradiotherapy. The improvement in prognosis appeared to result, at least in part, from the increase in the proportion of patients with better PS. Since the clinical feature and treatment outcome of patients with PCNSL can thus change with the era, historical control data should not be used in comparing different treatment modalities.

To explore the trade-off between dose assessment and imaging dose in respiratory gating with radiographic fluoroscopic imaging, we evaluated the relationship between dose assessment and fluoroscopic imaging dose in various gating windows, retrospectively.Four-dimensional (4D) CT images acquired for 10 patients with lung and liver tumours were used for 4D treatment planning for scanned carbon ion beam. Imaging dose from two oblique directions was calculated by the number of images multiplied by the air kerma per image. Necessary beam-on time was calculated from the treatment log file. Accumulated dose distribution was calculated. The gating window was defined as tumour position not respiratory phase and changed from 0-100% duty cycle on 4DCT. These metrics were individually evaluated for every case.For lung cases, sufficient dose conformation was achieved in respective gating windows [DWhen normal tissue doses are below the tolerance level, the gating window should be expanded to minimize imaging dose and treatment time. Advances in knowledge: The skin dose from imaging might not be counterbalanced to the OAR dose; however, imaging dose is a particularly important factor.

We report the structure and properties of a fullerene soot called “Nanom Black,” which is prepared by removing fullerenes from the soot formed in fullerene production. Nanom Black remarkably accelerates the regioselective tri-addition of phenylcopper reagent to C70, giving C70Ph3H at a reaction rate approximately 50-fold that in the absence of Nanom Black. Transmission electron microscopy, X-ray diffraction, and Raman data on Nanom Black are presented, and a mechanistic rationale is discussed.

Treatment of [CpFe(CO)2I] with terminal alkynes in the presence of catalytic amounts of dichlorobis(triphenylphosphine)palladium and copper iodide in aliphatic amine/THF results in Sonogashira-type carbon–iron bond formation to yield [CpFe(CO)2(Ctriple bond; length of mdashCR)] in good yields.

The purpose of this study was to evaluate the role of FDG-PET regarding the indication of preoperative carbon-ion radiotherapy (CIRT) for pancreatic cancer patients.Patients with resectable pancreatic cancer underwent preoperative CIRT. The impact of baseline SUVmax on prognosis for patients was assessed by analyzing correlations with distant metastasis-free survival (DMFS) and overall survival (OS).Out of 21 patients, local recurrence was observed in no patient and distant metastasis was found in 13 patients (62%). 1-year DMFS and OS in low-SUVmax group were significantly higher than those in high-SUVmax group (91% vs. 20% and 91% vs. 56%). SUVmax was significantly correlated with DMFS and OS.Our data indicated a significant correlation between SUVmax and DMFS. FDG-PET might be useful for determining the indication of preoperative short-course CIRT for patients with resectable pancreatic cancer.

Background/Aims: Staphylococcal enterotoxin B (SEB) acts as a superantigen binding to class II major histocompatibility complex proteins, and this complex stimulates T cells. The aim of this study was to investigate the pathogenic effects of SEB on hepatic injury and lethal shock in mice. Methods: SEB was administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver injury and levels of circulating cytokines were determined. In vitro cytokine production in response to SEB was also investigated. Results: Intraperitoneal administration of SEB (50 μg) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GaIN-sensitized mice, with no mortality on injection of up to 100 μg SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor α (TNF-α) levels reached a peak, followed by high levels of serum interferon-γ (IFN-γ) up to 10 hours after injection. Passive immunization with anti-TNF-α/β-neutralizing monoclonal antibody (mAb) protected GaIN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-γ-neutralizing mAb. SEB induced the production of TNF-α and IFN-γ in a dose-dependent manner from splenic mononuclear cells in vitro. Conclusions: The results show that SEB contributes to lethal shock associated with severe hepatic injury in GaIN-sensitized mice and suggest that TNF-α and IFN-γ produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.

In June 1994, the world's first clinical center offering carbon ion radiotherapy opened at the National Institute of Radiological Science (NIRS), Japan. Among several types of ion species, carbon ions were chosen for cancer therapy because they were judged to have the most optimal properties in terms of superior physical and biological characteristics. As of March 2010, 5,196 patients have been registered for carbon ion radiotherapy. Clinical results have shown that carbon ion radiotherapy has the potential to provide a sufficient radiation dose to the tumor, while having acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors as well as histologically non-squamous cell tumor types such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the unique properties of carbon ions, treatment with small fractions within a short treatment period has been successfully carried out for a variety of tumors. This means that carbon ion radiotherapy can offer treatment for larger numbers of patients than is possible with other modalities over the same time period.

Background: Mediastinal lymph node staging (N-staging) is essential to optimize the treatment in non-small cell lung cancer (NSCLC). Transesophageal endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has recently been introduced as a complementary method. However, in most reports, EUS-FNA has been performed in patients who have demonstrated enlarged lymph nodes (LNs) on CT findings. The yield of EUS/EUS-FNA in patients without enlarged mediastinal LNs by CT has so far only been evaluated in a few reports. Aims: Our aim was to compare the diagnostic accuracy of CT and EUS with or without EUS-FNA (EUS/EUS-FNA) prospectively, for N-stage in all patients with potentially resectable NSCLC, including patients with and without mediastinal LN enlargement based on CT findings. Methods: Eighty consecutive patients with potentially resectable NSCLC based on CT findings were enrolled in this prospective comparative study, and underwent EUS/EUS-FNA. Results: Pathological N-stage was established in 78 patients, while in another 2 cases, malignant pleural effusion was proven by EUS-FNA, and we avoided further N-staging. In the 78 patients, the prevalence of malignant mediastinal LNs was 21%. The accuracy of EUS/EUS-FNA (91%) was significantly higher than that of CT (71%). The negative predictive value of EUS/EUS-FNA was 90%. In addition, EUS-FNA identified 2 patients as N3 disease in 56 patients without mediastinal LN involvement on CT. Conclusions: EUS/EUS-FNA gave more accurate N-staging in patients with possibly resectable NSCLC than CT, and is thus considered to be useful to determine the optimal treatment strategy.

Background: Since the publication of the significant results of the Intergroup Study 0099 (IGS) in 1998, radical radiation therapy (RT) with concurrent and adjuvant chemotherapy has become the standard care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in the United States. An update in 2001 further strengthened the findings of the interim analysis, however, no prospective randomized trials other than this study have confirmed the feasibility of this strategy. Methods: We attempted to adopt the same combined modality treatment for three consecutive Japanese patients with locoregionally advanced NPC to evaluate its toxicity and efficacy. They were planned to receive radical RT concurrently with cisplatin every 3 weeks, and to receive adjuvant chemotherapy thereafter. Results: The hematological toxicities were mild and well tolerated in all three patients; however, they all experienced severe (grade 3 and/or 4) skin reactions, pharyngitis and dysphagia, which led to the discontinuation of the planned chemotherapy. They were able to complete RT without treatment breaks, and all three patients achieved complete response at the end of treatment. However, two experienced recurrences after 8 and 10 months, respectively, and died of their disease. Conclusions: Due to these severe acute adverse events, poor compliance and unsatisfactory outcomes, we have concluded that physicians should be careful in applying the concurrent chemoradiotherapy protocol employed by the IGS for locoregionally advanced Japanese NPC patients.