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Abstract Background Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. Methods This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0–48.0 Gy/2 fractions or 52.8–60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan–Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. Results In total, 76 patients with a median age of 71 years (range, 45–86 years) were evaluated. Among them, 68 had Child–Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5–180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7–79.4%), 32.7% (95% CI: 22.0–43.8%), and 8.9% (95% CI: 1.7–23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. Conclusions C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity.

Abstract Background and Aims Hepatocellular carcinoma (HCC) patients with Child‐Pugh (CP)‐B not eligible for surgery nor other focal therapy options due to impaired liver function, have very limited treatment options. This study aims to retrospectively investigate the toxicity and efficacy of Carbon‐ion radiotherapy (C‐ion RT) on HCC with CP‐B patients. Materials and Methods Patients with CP‐B, no extrahepatic metastasis, and treated with C‐ion RT between May 2000 and March 2020 were retrospectively extracted and included in this study. Results Sixty‐nine lesions of 58 patients were included. The median follow‐up duration was 20.5 (2.7–108) months. During follow‐up, recurrence was observed in 43 patients, including 2 local recurrences and 39 intrahepatic recurrences beyond the irradiation field. A grade 3 acute hepatotoxicity was observed in one patient during the observation period. No acute or late adverse event of grade ≥4 was observed. Overall survival was 80.4% and 46.0% at 1 and 2 years, respectively, and the median survival time was 22.6 months. Local control rate was 96.4% at both 1 and 2 years, and progression‐free survival was 38.6% and 6.9% at 1 and 2 years, respectively, with a median of 9.7 months. Conclusion The C‐ion RT showed low toxicity and good local effect in patients with HCC and CP‐B. Therefore, C‐ion RT could be an appropriate treatment for patients with HCC with poor liver function.

Abstract This study aimed to evaluate the uptake of the clinical effectiveness of [S-methyl-11C]-L-methionine positron emission tomography/computed tomography (MET PET/CT) in patients with esophageal cancer and to investigate MET PET/CT imaging parameters to assess early response for esophageal cancer with neoadjuvant carbon ion radiotherapy (CIRT). MET PET/CT scans were performed in nineteen patients before and 3 weeks after completion of CIRT. After Surgery, the effect of neoadjuvant CIRT was investigated by examining the relationship between each parameter of MET uptake and the histological assessment (grade and tumor residual ratio). Four parameters of MET uptake were the maximum and minimum standardized uptake values of pre and post CIRT (pre-SUVmax, pre-SUVmean, post-SUVmax, and post-SUVmean). MET PET/CT imaging of esophageal cancer was clearly demonstrated. The post-SUVmax was the most suitable parameter. When the cutoff value was set as post-SUVmax = 6.21, the sensitivity, the specificity, and the accuracy of Grades 3 were 100.0%, 63.6%, and 78.9%, respectively. And there was a positive relationship between the tumor residual ratio and post-SUVmax (R 2 = 0.38, p

Abstract Background Carbon-ion radiotherapy (CIRT) for esophageal cancer has been receiving significant attention given its high local control rates and minimal damage to normal tissues. However, the efficacy and safety of salvage surgery after CIRT for esophageal cancer remain unclear. We report the case of a patient who underwent salvage thoracoscopic surgery after CIRT. Case presentation A 51-year-old woman underwent upper gastrointestinal endoscopy and a type 0-IIa + 0-IIc esophageal squamous cell carcinoma located 27–29 cm from the patient’s incisors, classified as clinical stage I (T1bN0M0), was detected. She received CIRT (50.4 Gy [relative biological effectiveness, RBE]/12 fr) for localized esophageal cancer and achieved complete remission after 4 months. Six years after CIRT, follow-up endoscopic examination demonstrated a type 0-IIa + 0-IIc tumor in the previously treated area. In addition, a type 0-IIa lesion located 20–22 cm from the incisors was found. We diagnosed localized ESCC, classified as clinical stage I (T1bN0M0). Salvage thoracoscopic surgery was performed in the prone position with five access ports. Although the esophagus tightly adhered to the thoracic descending aorta and left main bronchus with severe fibrosis, the esophagus could be separated from the surrounding organs with careful forceps manipulation. The operation time and blood loss were 8 h 45 min and 253 mL, respectively. The patient was discharged from our hospital 17 days after the salvage surgery without any complications. Pathological findings revealed two squamous cell carcinomas. Both tumors were localized in the lamina propria mucosa, and lymph node metastasis was not detected. The tumors were diagnosed as pathological stage IA (pT1aN0M0) according to the TNM criteria. Moreover, pathological examinations showed severe fibrosis of the previously irradiated tissues compared to the normal esophagus located outside of the irradiation field. Following the surgery, the patient had no recurrence for 1 year and 6 months. Conclusions Thoracoscopic radical esophagectomy can be performed as salvage surgery. Careful and discreet surgery is integral to perform salvage surgery after CIRT since CIRT may cause severe adhesions and fibrosis in the irradiated field.

Purpose: Carbon ion beams have several physical and biological advantages compared with conventional radiation for cancer therapy. The objective of this study is to evaluate the safety and effectiveness of 2-fraction carbon ion radiation therapy (CIRT) in patients with hepatocellular carcinoma (HCC). Methods and Materials: Between December 2008 and March 2013, 57 patients with localized HCC were treated with CIRT at a total dose of 45 Gy (relative biological effectiveness) in 2 fractions and retrospectively analyzed after long-term observation. The main endpoints of this study were treatment-related toxicity and local tumor control. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Changes in the Child-Pugh score from before to after CIRT were also examined to evaluate hepatic toxicity. Local control was defined as no progression of the irradiated lesion according to the modified Response Evaluation Criteria in Solid Tumors. Results: The median age of the patients was 75 years (range, 49-89 years). Of these patients, 41 had a newly diagnosed lesion, and 16 had residual or recurrent lesions after previous treatments. The median follow-up duration was 54 months (range, 7-103 months). All surviving patients were followed for more than 51 months. Two patients experienced grade 3 acute skin reactions, but no other grade 3 or higher toxicities were observed in any organ. No patient exhibited an increase in the Child-Pugh score of 2 or more points after CIRT. The local tumor control rates at 1, 3, and 5 years were 98%, 91%, and 91% after CIRT, respectively. All lesions that failed to respond to previous treatments were successfully controlled by CIRT. The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 45%, respectively. Conclusions: Two-fraction CIRT was a well-tolerated and effective treatment for patients with HCC.

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 (≥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.

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 s-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Treatment of aryliron complexes [CpFe(CO)2Ar] with organolithium reagents RLi in THF affords the corresponding ketones RCOAr. The reaction, wherein the aryliron complexes serve as arylcarbonyl cation equivalents, would begin with nucleophilic addition of RLi to one of the carbonyl ligands to form acyliron [CpFe(CO)(RCO)Ar] without lithiation of the Cp ring. [ABSTRACT FROM AUTHOR]

Abstract Purpose  Progress of the novel carbon ion radiotherapy (CIRT) in the treatment of cancers has created the need for a method to accurately evaluate the response. We investigated whether l-[11C]methyl-methionine (11C-methionine) uptake at pre- and post-CIRT could be an early response predictor in patients with pelvic recurrence of rectal cancer. Procedures   11C-Methionine-positron emission tomography (PET) was performed prospectively in 53 patients with pelvic recurrence of rectal cancer before CIRT, and 48 patients were performed 11C-methionine PET at 1 month after CIRT. 11C-Methionine tumor uptake was measured by the tumor to muscle ratio (T/M ratio). The T/M ratios were evaluated in relation to clinical outcomes such as local re-recurrence, distant metastasis, and survival. The response to CIRT was also judged by computed tomography (CT) and magnetic resonance imaging (MRI). 11C-Methionine PET judgment was compared with CT/MRI judgment regarding the relevance to clinical outcome. Results  Baseline T/M ratio was 5.27 ± 1.90 (mean ± SD) in patients without developing local re-recurrence and 7.66 ± 3.17 in patients with local re-recurrence (p = 0.023, Mann–Whitney U test). Post-CIRT T/M ratios were 3.10 ± 1.28 in patients without local re-recurrence and 6.15 ± 2.98 in patients with local re-recurrence (p = 0.006, Mann–Whitney U test). By Kaplan–Meier analysis with log-rank test, patients with a baseline T/M ratio of ≦7.6 or a post-CIRT T/M ratio of ≦5.0 had significant lower pelvic re-recurrence rate. However, the percent change (reduction rate) from baseline to post-CIRT T/M ratio did not have significant relation to pelvic re-recurrence. There were no significant differences between 11C-methionine results (baseline T/M ratio, post-CIRT T/M ratio and percent change) and other clinical parameters (distant metastasis and survival). Conclusion   11C-methionine-PET can be used for early prediction of local re-recurrence after CIRT. Because CIRT is local therapy, 11C-methionine-PET cannot predict distant metastasis or survival after CIRT. [ABSTRACT FROM AUTHOR]

Treatment of aryliron complexes [CpFe(CO)2Ar] with styrenes in boiling xylene affords the corresponding stilbenes. The aryliron complexes, which become active upon heating, serve as arylating agents in the reaction. [ABSTRACT FROM AUTHOR]

Transmetalation between [CpFe(CO)2I] and arylzinc reagents or arylboronic acids under palladium catalysis yields the corresponding aryliron complexes [CpFe(CO)2Ar]. The reactions offer easy and reliable accesses to a variety of [CpFe(CO)2Ar] species bearing a functionalized aryl group. [ABSTRACT FROM AUTHOR]

Palladium-catalyzed transmetalation between [CpFe(CO) 2I] and aryl Grignard reagents emerges as a new method for the synthesis of [CpFe(CO) 2Ar]. The aryliron complexes thus formed are useful arylmetal reagents that become active upon oxidation or UV irradiation. [ABSTRACT FROM AUTHOR]

Transmetalation between [CpFe(CO)2I] and aryltin reagents in the presence of copper salts yields the corresponding aryliron complexes [CpFe(CO)2Ar]. The high functional group compatibility of this copper-mediated reaction enables us to obtain [CpFe(CO)2Ar] having an acetyl or formyl group, which cannot be prepared by the previous methods with arylzinc or arylboron reagents under palladium catalysis. [ABSTRACT FROM AUTHOR]

Purpose Pencil beam scanning offers excellent conformity, but is sensitive to organ motion. We conducted a simulation study to validate our rescanning approach in combination with gating in the irradiation of liver tumors. Materials and methods 4DCT imaging was performed under free-breathing conditions in 30 patients with hepatocellular carcinoma. Dose distributions for a two-field approach were calculated for layered phase controlled rescannings (PCR) under organ motion conditions. A total dose of 45 Gy(RBE) was delivered to respective field-specific target volumes (FTVs) in two fractions, each composed of two orthogonal uniform fields of 11.25 Gy(RBE) at beam angles of either 0° and 90° or 0° and 270°. The number of rescannings was changed from 1 to 10. Results Good dose conformity was achieved with 4x PCR or more, and over 95% of the prescribed dose was delivered to the CTV independent of the use of gating. D95, Dmax/min and dose homogeneity were similar with or without gating, whereas V10 dose to the liver as well as maximal doses to healthy tissue (esophagus and cord) were about 40% lower with gating. However, total time increased by about 50% with gating. Conclusions Gated rescanning provides good target coverage and homogeneity with maximal sparing of healthy tissue. Our results suggest that carbon-ion pencil beam scanning may soon be available for the safe treatment of liver tumors. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with locally recurrent rectal cancer., Patients and Methods: We conducted a phase I / II dose escalation of carbon ion radiotherapy. One hundred twelve patients with 117 sites of locally recurrent cancer receiving carbon ion radiotherapy were analyzed., Results: None of 112 patients experienced National Cancer Institute-Common Toxicity Criteria grade 3 to 5 acute reactions. The local control rate in patients treated with 67.2 GyE, 70.4 GyE and 73.6 GyE in the present study was 70%, 89% and 97% at 5 years, respectively. The overall survival rates in patients treated with 73.6 GyE were 72% at 3 years and 40% at 5 years., Conclusion: Carbon ion radiotherapy seems to be a safe and effective modality in the management of locally recurrent rectal cancer, providing good local control and offering a survival advantage without unacceptable morbidity.