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

The synergistic merger of a thiazolium N-heterocyclic carbene (NHC) catalyst and a palladium–bisphosphine catalyst enabled the allylation of aldehyde acyl anions using allylic carbonates as electro...

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.

Benzylation and allylation of aldehyde acyl anions were enabled by the merger of a thiazolium N-heterocyclic carbene (NHC) catalyst and a palladium/bisphosphine catalyst in a synergistic manner. Owing to the mildness of the reaction conditions, various functional groups were tolerated in the substrates.

The first Csp3-Csp2 cross-coupling using aldehydes as latent α-alkoxyalkyl anion equivalents has been achieved. The synergistic palladium/copper-catalyzed reaction of aromatic aldehydes and aryl bromides with a silylboronate afforded the three-component coupling products, silyl-protected benzhydrol derivatives. The reaction pathway involves the catalytic formation of a nucleophilic α-silyloxybenzylcopper(i) species followed by its palladium-catalyzed cross-coupling with aryl bromides.

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.

The treatment of benzylallene-substituted internal alkynes with [RhCl(CO)2 ]2 effects a novel cycloisomerization by C(sp(2) )-H bond activation to produce hexahydrophenanthrene derivatives. The reaction likely proceeds through consecutive formation of a rhodabicyclo[4.3.0] intermediate, σ-bond metathesis between the C(sp(2) )-H bond on the benzene ring and the C(sp(2) )-Rh(III) bond, and isomerization between three σ-, π-, and σ-allylrhodium(III) species, which was proposed based on experiments with deuterated substrates.

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.

Purpose To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m2 under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. Results Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m2. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m2) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

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.

Background & aims Carbon-ion radiation therapy has shown encouraging results in hepatocellular carcinoma patients in single-centre studies. We evaluated the effectiveness and safety of short-course carbon-ion radiation therapy for hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion Radiation Oncology Study Group. Methods Consecutive hepatocellular carcinoma patients who were treated with carbon-ion radiation therapy in four or fewer fractions at four Japanese institutions between April 2005 and November 2014 were analysed retrospectively. The primary outcome was overall survival; secondary outcomes were local control rate, treatment-related toxicity and radiation-induced liver disease. Results A total of 174 patients were included in this study. Prescribed carbon-ion radiation therapy doses were (relative biological effectiveness): 48.0 Gy in two fractions (n = 46), and 52.8 Gy (n = 108) and 60.0 Gy (n = 20) in four fractions. The median follow-up period was 20.3 (range, 2.9-103.5) months. The overall survival and local control rates at 1, 2 and 3 years were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status 1-2, Child-Pugh class B, maximum tumour diameter ≥3 cm, multiple tumours and serum alpha foetoprotein level >50 ng/mL were significant prognostic factors of overall survival. No treatment-related death occurred during the follow-up period. Grades 3 or 4 treatment-related toxicities were observed in 10 patients (5.7%); radiation-induced liver disease was observed in three patients (1.7%). Conclusions Short-course carbon-ion radiation therapy is a safe, effective and potentially curative therapy for hepatocellular carcinoma.

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.

Treatment of the allene-ene-yne substrates with [{RhCl(CO)2}2] effected the intramolecular [2+2+2]-type ring-closing reaction to produce various of tri- and tetracyclic derivatives containing a cyclopropane ring. The reaction is highly stereoselective as well as stereospecific with good to excellent yields.

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.

We previously reported that an adequate number of simple layered phase-correlated rescanning (PCR) irradiations improve dose conformation to a moving target. However, if PCR is not completed within a single gating window due to the particular irradiation specifications selected in advance and/or layer size, the iso-energy layer is completed using next gating window, and the effect of rescanning is effectively nullified. To solve this problem, we developed extended PCR irradiation. Extended PCR is conceptually based on simple PCR. It differs in that the dose rate is adjusted to irradiate the number of rescans within multiple gating windows when simple PCR is not finished within a single gating window. This process is repeated until the total prescribed dose is given. Here, 4DCT imaging was performed under free-breathing conditions in 10 patients with hepatocellular carcinoma. 4D dose distributions for a single field approach were performed with simple PCR and extended PCR using 4DCT. A total dose of 11.25 Gy(RBE) was administered to the field-specific target volume. The number of rescans was changed from 1 to 10. Respiratory gating of a 30% duty cycle around exhalation was applied. Dose assessment metrics (CTV-D95, CTV-Dmin, CTV-Dmax) with PCR improved with an increasing number of rescans, and largely plateaued at five or more rescans. Minimum D95 and Dmin values, and maximum Dmax and HI values fluctuated at odd and even numbers of rescans. Extended PCR improved all dose assessment metrics whereas PCR did not. Values with extended PCR were mostly constant with three or more rescans, or in other words independent of the number of rescans. Extended PCR improved dose conformation to a moving target with greater efficacy than simple PCR when more than two gating windows were necessary. Extended PCR can be applied to irradiation machines having a low maximum dose rate.

The efficient Rh(I)-catalyzed cycloisomerization of benzylallene-alkynes produced the tricyclo[9.4.0.0(3,8)]pentadecapentaene skeleton through a C(sp2)-H bond activation in good yields. A plausible reaction mechanism proceeds via oxidative addition of the acetylenic C-H bond to Rh(I), an ene-type cyclization to the vinylidenecarbene-Rh(I) intermediate, and an electrophilic aromatic substitution with the vinylidenecarbene species. It was proposed based on deuteration and competition experiments.

Objective This study aims to assess the usefulness of monitoring serum α-fetoprotein (AFP) levels for predicting recurrence patterns in patients with hepatocellular carcinoma (HCC) treated with carbon-ion radiotherapy.

The treatment of benzylallene-substituted internal alkynes with [RhCl(CO)2 ]2 effects a novel cycloisomerization by C(sp(2) )-H bond activation to produce hexahydrophenanthrene derivatives. The reaction likely proceeds through consecutive formation of a rhodabicyclo[4.3.0] intermediate, σ-bond metathesis between the C(sp(2) )-H bond on the benzene ring and the C(sp(2) )-Rh(III) bond, and isomerization between three σ-, π-, and σ-allylrhodium(III) species, which was proposed based on experiments with deuterated substrates.

Background The safety and effectiveness of carbon-ion radiotherapy (CIRT) for isolated para-aortic lymph node (PALN) metastasis was evaluated retrospectively. Methods CIRT for isolated PALN metastasis from CRC was performed in 34 cases from June 2006 to August 2015 in our institute. A median dose of 52.8 Gy(RBE) (range, 48-52.8 Gy(RBE)) was delivered with a median daily dose of 4.4 Gy(RBE) (range, 4.0-4.4 Gy(RBE)). Results The median follow-up duration for all patients was 24.4 months (range, 7-82.8 months). There were 13 cases (38.2%) who achieved complete response after treatment. The local control rates at 2 and 3 years were 70.1% and 70.1%, respectively. The overall survival rates at 2 and 3 years were 83.3% and 63.0%, respectively. The 3-year survival rates for Stage I-III were 68.7%, while those for Stage IV was 0%. The overall survival of cases with rectal cancer or with high CA19-9 values pre-CIRT tended to be worse. The median survival period was 41.7 months. Twelve of the 34 patients survived for more than 3 years. There were no adverse effects of Grade 3 or higher. Conclusions CIRT for isolated PALN recurrence after curative resection for CRC appears effective and safe, and it is considered a promising therapy.

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 title reaction, promoted by a soft Lewis acid/hard Broensted base cooperative catalyst, affords homoallylic alcohols with a Z-configured α,β-unsaturated nitrile from aromatic aldehydes with electron-donating substituents, allowing for rapid access to unsaturated γ-valerolactones like (VIII), which is a key intermediate in the synthesis of fostriecin.

BACKGROUND: The authors evaluated the tolerance and efficacy of carbon-ion radiotherapy (CIRT) as a short-course, preoperative treatment and determined the recommended dose needed to reduce the risk of postoperative local recurrence without excess injury to normal tissue. METHODS: Patients radiographically defined with potentially resectable pancreatic cancer were eligible. A preoperative, short-course, dose-escalation study was performed with fixed 8 fractions in 2 weeks. The dose of irradiation was increased by 5% increments from 30 grays equivalents (GyE) to 36.8 GyE. Surgery was to be performed 2 to 4 weeks after the completion of CIRT. RESULTS: The study enrolled 26 patients. At the time of restaging after CIRT, disease progression with distant metastasis or refusal ruled out 5 patients from surgery. Twenty-one of 26 patients (81%) patients underwent surgery. The pattern of initial disease progression was distant metastasis in 17 patients (65%) and regional recurrence in 2 patients (8%). No patients experienced local recurrence. The 5-year survival rates for all 26 patients and for those who underwent surgery were 42% and 52%, respectively. CONCLUSIONS: Preoperative, short-course CIRT followed by surgery is feasible and tolerable without unacceptable morbidity. Cancer 2013. © 2012 American Cancer Society.

Background Carbon-ion radiotherapy (CIR) has been under development. We report the results of a phase I/II clinical trial of preoperative CIR for esophageal squamous cell carcinoma (ESCC). Methods Thirty-one thoracic ESCC patients were enrolled. They were first treated with CIR. The radiation dose was escalated from the initial dose of 28.8 GyE up to 36.8. Four to 8 weeks after CIR followed by clinical evaluation of the therapy, surgery was performed. Thereafter, a pathological evaluation was made. Results Acute toxicity was not seen except in one case (3.2%), and there were no late toxicities. Throughout the study period, there were no cases of withdrawal due to the effects of preoperative CIR. Twelve out of 31 (38.7%) patients achieved a clinical complete response (CR) and 13 patients (41.9%) achieved a partial response. Twelve out of 31 patients (38.7%) achieved a pathological CR. The overall 1-, 3-, and 5-year survival rates in the stage I cases were 91%, 81%, and 61%, and was 100%, 85%, and 77% for the stage II, and 71%, 43%, and 29% for the stage III cases, respectively. Conclusions CIR showed strong local tumor control and is highly effective as a neoadjuvant therapy without severe adverse events. J. Surg. Oncol. 2012; 105:750–755. © 2011 Wiley Periodicals, Inc.

Recently, transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been evaluated for mediastinal nodal staging (N staging) of lung cancer, as this technique is less invasive than mediastinoscopy and possibly more accurate than 18F-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). However, EUS-FNA does not provide access to pretracheal and hilar lymph nodes. More recently, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been introduced as a novel technique for accessing pretracheal and hilar lymph nodes. Although the combined endoscopic approach of EUS-FNA and EBUS-TBNA is presumably more accurate than PET-CT, only a few reports have quantitatively evaluated its diagnostic ability. Therefore, we prospectively assessed the diagnostic yield of this combined endoscopic approach for mediastinal N staging of lung cancer.A consecutive series of 120 patients with suspected resectable lung cancer on CT findings underwent PET-CT and combined EUS-FNA/EBUS-TBNA. The accuracy and other diagnostic indices of the combined approach in mediastinal N staging were compared with those of PET-CT.Among the enrolled patients, a final pathological N stage was established in 110 patients. The accuracy of the combined approach using EUS-FNA and EBUS-TBNA was significantly higher than that of PET-CT (90.0 % vs. 73.6 %; P0.0001). The sensitivity, specificity, and positive and negative predictive values were respectively 71.8 %, 100 %, 100 %, and 86.6 % for the combined approach vs. 47.4 %, 87.5 %, 66.7 %, and 75.9 % for PET-CT.The combined endoscopic approach using EUS-FNA and EBUS-TBNA provided excellent diagnostic performance. Therefore, this approach is strongly recommended before surgery or mediastinoscopy to avoid futile thoracotomy and surgical intervention.

Background and purpose To compare the efficacy and toxicity of short-course carbon ion radiotherapy (C-ion RT) for patients with hepatocellular carcinoma (HCC) in terms of tumor location: adjacent to the porta hepatis or not. Materials and methods The study consisted of 64 patients undergoing C-ion RT of 52.8GyE in four fractions between April 2000 and March 2003. Of these patients, 18 had HCC located within 2cm of the main portal vein (porta hepatis group) and 46 patients had HCC far from the porta hepatis (non-porta hepatis group). We compared local control, survival, and adverse events between the two groups. Results The 5-year overall survival and local control rates were 22.2% and 87.8% in the porta hepatis group and 34.8% and 95.7% in the non-porta hepatis group, respectively. There were no significant differences ( P= 0.252, P =0.306, respectively). Further, there were no significant differences in toxicities. Biliary stricture associated with C-ion RT did not occur. Conclusions Excellent local control was obtained independent of tumor location. The short-course C-ion RT of 52.8GyE in four fractions appears to be an effective and safe treatment modality in the porta hepatis group just as in the non-porta hepatis group.

Background and purpose To examine whether liver volume changes affect prognosis and hepatic function in patients treated with carbon ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC). Material and methods Between April 1995 and March 2003, among the cases treated with CIRT, 43 patients with HCC limited to the right hepatic lobe were considered eligible for the study. The left lateral segment was defined as the non-irradiated region. Liver volume was measured using contrast CT at 0, 3, 6, and 12months after CIRT. We examined serum albumin, prothrombin activity, and total bilirubin level as hepatic functional reserve. Results After CIRT, the non-irradiated region showed significant enlargement, and enlarged volume of this region 3months after CIRT ⩾50cm 3 was a prognostic factor. The 5-year overall survival rates were 48.9% in the larger enlargement group (enlarged volume of non-irradiated region 3months after CIRT ⩾50cm 3 ) and 29.4% in the smaller enlargement group (as above, 3 ). The larger enlargement group showed better hepatic functional reserve than the smaller enlargement group 12months after CIRT. Conclusions This study suggests that compensatory enlargement in the non-irradiated liver after CIRT contributes to the improvement of prognosis.